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Intelligent Design, the best explanation of Origins » Molecular biology of the cell » Development biology » Evolution: Where Do Complex Organisms Come From?

Evolution: Where Do Complex Organisms Come From?

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Where Do Complex Organisms Come From?

http://reasonandscience.catsboard.com/t2316-evolution-where-do-complex-organisms-come-from

Based on evidence seen in biochemistry on a molecular level, we can now say affirmatively and conclusively, that Darwins theory of evolution by natural selection in regards of first degree macroevolutionary level has been falsified.

The real mechanisms that explain biodiversity and complex organismal architecture is preprogrammed instructional complex INFORMATION encoded in various genetic and epigenetic languages and communication by various signalling codes through various signalling networks

That brings us to the origin by an intelligent designer.

Pinpointing what REALLY defines body architecture, the orchestration of organism development, cell shape and body form and the mechanisms of adaptation and primary speciation, and exposing the correct explanation of biochemical mechanisms of biodiversity is the holy grail of biological sciences. Preprogrammed codified information and signalling replaces Darwin's theory and its various subsequent adaptations, extensions, and new proposals like the modern extended synthesis or the so-called " third way ". The true mechanism is " Biochemical systems programming and signalling", and special creation of species and/or kinds by an intelligent powerful creator. Long periods of time and gradual, evolutionary development is not possible, face the fact that cells and organisms work like gigantic interlocked machines and factory complexes, where in any case, if one tiny part is missing, nothing goes. Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. No glycine amino acids, no pyrimidines, no DNA - no life. No Watson Crick base pair fine-tuning, no DNA - no life. No ribosomal mechanism for amino acid amide bondage, no proteins, no life. No nitrogenase enzymes to fix nitrogen in an energy demanding, triple bond breaking process, no ammonia, required to make amino acids - no nitrogen cycle - no advanced life. No chlorophylls, no absorption of light to start photosynthesis, no starch and glucose - cells will have no food supply to sustain complex organisms - no advanced life on earth. No rubisco, no fix of CO2, no hydrocarbons - no advanced life. No counterion in retinal, and rhodopsin could not receive visible light - and there would be no vision on earth by any organism.


1. The Gene regulation network orchestrates gene expression
2. Various signalling pathways generate Cell types and patterns
3. At least 23 Epigenetic Codes are multidimensional and perform various tasks essential to cell structure and development
4. Cell-Cell communication in various forms, especially important for animal development
5. Chromatin dance in the nucleus through extensile motors affect transcription and gene regulation
6. Post-transcriptional modifications (PTMs) of histones affect gene transcription
7. The DNA methylation code is like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on.
8. Homeobox and Hox genes determine the shape of the body.
9. Noncoding DNA  ( Junk DNA ) is transcribed into functional non-coding RNA molecules and switches protein-coding genes on or off.
10.  Transposons and Retrotransposons regulate genes
11. Centrosomeplay a central role in development
12. The precise arrangement of Cytoskeletal arrays provides critical structural information.
13. Membrane targets provide crucial information—spatial coordinates—for embryological development.
14. Ion Channels and Electromagnetic Fields influence the form of a developing organism
15. The Sugar Code forms information-rich structures which influence the arrangement of different cell types during embryological development.
16. Egg-polarity genes encode macromolecules deposited in the egg to organize the axes
17. Hormones  are special chemical messengers for development



1. Biological sciences have come to discover in the last decades that major morphological innovation, development and body form are based on at least 16 different, but integrative mechanisms, the interplay of genes with the gene regulatory network, Trans and Retrotransposons, so-called Junk DNA, gene splicing and recombination, and at least two dozen epigenetic informational code systems, some, like the glycan ( sugar) code, far more complex than the genetic code, on the membrane - exterior side of cells, Post-transcriptional modifications (PTMs) of histones, hormones, Ion Channels and Electromagnetic Fields that are not specified by nuclear DNA, Membrane targets and patterns, Cytoskeletal arrays, Centrosomes, and inheritance by cell memory which is not defined through DNA sequences alone.

2. These varied mechanisms orchestrate gene expression, generate Cell types and patterns, perform various tasks essential to cell structure and development, are responsible for important tasks of organismal development, affect gene transcription, switch protein-coding genes on or off,  determine the shape of the body, regulate genes, provide critical structural information and spatial coordinates for embryological development,  influence the form of a developing organism and the arrangement of different cell types during embryological development, organize the axes, and act as chemical messengers for development

3. Neo-Darwinism and the Modern Synthesis have proposed traditionally a gene-centric view, a scientific metabiological proposal going back to Darwin's " On the origin of species ", where first natural selection was proposed as the mechanism of biodiversity, and later,  gene variation defining how bodies are built and organized. Not even recently proposed alternatives, like the third way, neutral theory, inclusive fitness theory, Saltationism, Saltatory ontogeny, mutationism, Genetic drift, or combined theories, do full justice by taking into account all organizational physiological hierarchy and complexity which empirical science has come to discover.

4. Only a holistic view, namely structuralism and systems biology, take into account all influences that form cell form and size, body development and growth, providing adequate descriptions of the scientific evidence. The BIG ( umbrella ) contributor to explain organismal complexity is preprogrammed instructional complex INFORMATION encoded in various languages and communication through signalling through various signalling networks  that act  on a structural level, which are pre-instructed to respond to environmental cues, development, and nutrition demands, and they are apt to communicate, crosstalk, signal, regulate, govern, control, recruit, interpret, recognize, orchestrate, elaborate strategies, guide and so forth. All codes, blueprints, and languages are inventions by intelligence. Therefore, the genetic and epigenetic codes and signalling networks and the instructions to build cells and complex biological organisms were most likely created by an intelligent agency.


Biological cells and organisms are characterized by Irreducible complexity and hierarchical top-down systems interdependence, which is understood as irreducible functional systems complexity. And such is specified by genetic and epigenetic informational codes and signals, used to set up and create front-loaded instructional blueprints, which direct how bodies are built, but also how life can self-correct, adapt to the environment and evolve. It is perfectly comparable to how a blueprint instructs to make machines and factories, and industries. Such things come undoubtedly from preexisting intelligence.

To understand the major trends in animal diversity and if the various kinds of morphology are due to evolution, we must first understand how animal form is generated. As science has unravelled, the make of body form, phenotype, and organismal architecture is due to several genetic and principally, epigenetic interlocked and interconnected mechanisms. The modern, extended evolutionary synthesis does not take into consideration all relevant factors. Structuralism proposes that complex structure emerges holistically from the dynamic interaction of all parts of an organism. It denies that biological complexity can be reduced to natural selection, gene drift and gene flow, and argues that pattern formation is driven principally by multilevel processes that involve various functional units, working in an interdependent manner, pre-programmed to respond to ecological and environmental cues and conditions, food resource availability, and development programs.  Various genetic and epigenetic Codes, an integrated understanding of the structural and functional aspects of epigenetics and several signalling pathways, nuclear architecture during differentiation, chromatin organisation, morphogenetic fields, amongst many other mechanisms.



The Gene regulation network
Epigenetics refers to heritable changes in gene expression that occur without alteration in DNA sequence. These changes may be induced spontaneously, induced by environmental factors or as a consequence of specific mutations. There are two primary and interconnected epigenetic mechanisms: DNA methylation and covalent modification of histones. 42 . In addition, it has become apparent that non-coding RNA is also intimately involved in this process. The different mechanisms that control epigenetic changes do not stand alone, and there are a clear interconnection and interdependency between:
 
Cell type and patterns found in the animal kingdom, are generated by following signalling pathways:

- Hedgehog (Hh)
- Wingless related (Wnt)
- Transforming growth factor-β (TGF-β)
- Receptor tyrosine kinase (RTK)
- Notch
- Janus kinase (JAK)/signal transducer  
- Activators of transcription (STAT) protein kinases
- Nuclear hormone pathways
- Bone morphogenetic proteins (BMP)
- Epidermal growth factor receptors (EGFR)
- Fibroblast growth factors (FGF)
- DNA methylation 
- Histone modification and incorporation of histone variants
- Chromatin remodelling in Eukaryotic Cells  
- Non-coding RNA-mediated epigenetic regulation

Epigenetic Codes:
The Genomic regulatory Code
The Splicing Codes
The Metabolic Code
The Signal Transduction Codes
The Signal Integration Codes
The Histone Code
The Tubulin Code
The Sugar Code
The Glycomic Code
The non-ribosomal code
The Calcium Code
The RNA code
A domain substrate specificity code of Nonribosomal peptide synthetases (NRPS)
The DNA methylation Code
The coactivator/corepressor/epigenetic code
The transcription factor code
The post-translational modification code for transcription factors
The HOX Code
The Synaptic Adhesive Code
The Apoptosis Code
The Ubiquitin Code
The bioelectric code
The transcriptional cis-regulatory code


Genes involved in Cell-Cell communication and transcriptional control are especially important for animal development
What are the genes that animals share with one another but not with other kingdoms of life? These would be expected to include genes required specifically for animal development but not needed for unicellular existence. Comparison of animal genomes with the genome of budding yeast—a unicellular eukaryote— suggests that three classes of genes are especially important for multicellular organization.

The first class includes genes that encode proteins used for cell–cell adhesion and cell signaling; hundreds of human genes encode signal proteins, cell-surface receptors, cell adhesion proteins, or ion channels that are either not present in yeast or present in much smaller numbers.

The second class includes genes encoding proteins that regulate transcription and chromatin structure: more than 1000 human genes encode transcription regulators, but only about 250 yeast genes do so. The development of animals is dominated by cell–cell interactions and by differential gene expression.

The third class of noncoding RNAs has a more uncertain status: it includes genes that encode microRNAs (miRNAs); there are at least 500 of these in humans. Along with the regulatory proteins, they play a significant part in controlling gene expression during animal development, but the full extent of their importance is still unclear.

Chromatin dance in the nucleus through extensile motors
Transcription and gene regulation Genome topology has emerged as a key player in all genome functions. Although a contribution of local genome looping in transcription has long been appreciated, recent observations have revealed the importance of long-range interactions, and genome-wide studies have uncovered the universal nature of such regulatory genome topology interactions in gene regulation. Several types of chromosomal interactions, either in the form of loops between sequences on the same chromosomes or interchromosomal interactions, have emerged as key mechanisms in gene regulation.
The nature of genome topology is very precise, and so its regulatory functions in gene expression and genome maintenance. The emerging picture is one of extensive self-enforcing feedback between activity and spatial organization of the genome, suggestive of a self-organizing and self-perpetuating system that uses epigenetic dynamics to regulate genome function in response to regulatory cues and to propagate cell-fate memory

Post-transcriptional modifications (PTMs) of histones affect gene transcription
According to the histone code hypothesis, the pattern of histone modification is recognized by proteins much like a language or code. One pattern of histone modification may attract proteins that inhibit transcription. Alternatively, a different combination of histone modifications may attract proteins, such as ATP-dependent chromatin-remodeling complexes, that promote gene transcription. In this way, the histone code plays a key role in accessing the information within the genomes of eukaryotic species. Post-translational modifications (PTMs) of histones provide a fine-tuned mechanism for regulating chromatin structure and dynamics.  In addition to combinatorial PTMs that function together both synergistically and antagonistically, there is now an appreciation for PTM asymmetry within individual nucleosomes, novel types of PTMs with unique functions, nucleosomes bearing histone variants, and nuclear compartmentalization events that are all contributing to the final output of chromatin organization and function

The DNA methylation code and language
One of the best known epigenetic mechanisms is DNA methylation in which a small molecule (a methyl group) is added to the DNA macromolecule at particular locations. Like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on. This DNA methylation is accomplished via the action of a protein machine that adds the methyl group at precisely the right location in the DNA strand. Methylation of DNA occurs at certain target sites along the DNA sequence where specific short DNA sequences appear. These sequences are found by special proteins as they move along the DNA. The special proteins search for these sequences and add a methyl group to the adenine base that appears within the sequence. The protein binds to the DNA, twists the helix so the adenine base rotates into a precisely shaped pocket in the protein, and the protein then facilitates the transfer of the methyl group from a short donor molecule for example to adenine.

Homeobox and Hox Genes
This family of related genes determines the shape of the body. It subdivides the embryo along the head-to-tail axis into fields of cells that eventually become limbs and other structures.  Starting as a fertilized egg with a homogeneous appearance, an embryo made of skin, muscles, nerves and other tissues gradually arises through the division of cells. Long before most cells in the emerging body begin to specialize, however, a plan that designates major regions of the body-the head, the trunk, the tail and so on is established. This plan helps seemingly identical combinations of tissues arrange themselves into distinctly different anatomical structures, such as arms and legs. Individual genes mediate some of the developmental decisions involved in establishing the embryonic body plan.

" Junk DNA "
MicroRNAs--"Once Dismissed as Junk"--Confirmed To Have Important Gene Regulatory Function In 2008 Scientific American noted that microRNAs were "once dismissed as junk" and said the following:
Tiny snippets of the genome known as microRNA were long thought to be genomic refuse because they were transcribed from so-called "junk DNA," sections of the genome that do not carry information for making proteins responsible for various cellular functions. Evidence has been building since 1993, however, that microRNA is anything but genetic bric-a-brac. Quite the contrary, scientists say that it actually plays a crucial role in switching protein-coding genes on or off and regulating the amount of protein those genes produce.

Transposons and Retrotransposons
striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.

Centrosomes
Centrosomes play a central role in development: a frog egg can be induced to develop into a frog merely by injecting a sperm centrosome—no sperm DNA is needed. Another non-genetic factor involved in development is the membrane pattern of the egg cell. 

Cytoskeletal arrays 
The precise arrangement of microtubules in the cytoskeleton constitutes a form of critical structural information. neither the tubulin subunits, nor the genes that produce them, account for the differences in the shape of the microtubule arrays that distinguish different kinds of embryos and developmental pathways. Instead, the structure of the microtubule array itself is, once again, determined by the location and arrangement of its subunits, not the properties of the subunits themselves. Jonathan Wells explains it this way: “What matters in [embryological] development is the shape and location of microtubule arrays, and the shape and location of a microtubule array is not determined by its units.” Directed transport involves the cytoskeleton, but it also depends on spatially localized targets in the membrane that are in place before transport occurs. Developmental biologists have shown that these membrane patterns play a crucial role in the embryological development of fruit flies.

Signaling between cells orients the mitotic spindle 
In multicellular animals, cell communication sometimes serves to orient the direction in which cells divide. Control of division orientation has been proposed to be critical for partitioning developmental determinants and for maintaining epithelial architecture. Surprisingly, there are few cases where we understand the mechanisms by which external cues, transmitted by intercellular signaling, specify the division orientation of animal cells. One would predict that cytosolic molecules or complexes exist that are capable of interpreting extrinsic cues, translating the positions of these cues into forces on microtubules of the mitotic spindle. In recent years, a key intracellular complex has been identified that is required for pulling forces on mitotic spindles in Drosophila, C. elegans and vertebrate systems. One member of this complex, a protein with tetratricopeptide repeat (TPR) and GoLoco (Gα-binding) domains, has been found localized in positions that coincide with the positions of spindle-orienting extracellular cues. Do TPR-GoLoco proteins function as conserved, spatially-regulated mediators of spindle orientation by intercellular signalling? Here, we review the relevant evidence among cases from diverse animal systems where this protein complex has been found to localize to specific cell-cell contacts and to be involved in orienting mitotic spindles.

Membrane targets
Preexisting membrane targets, already positioned on the inside surface of the egg cell, determine where these molecules will attach and how they will function. These membrane targets provide crucial information—spatial coordinates—for embryological development.

Ion Channels and Electromagnetic Fields
Experiments have shown that electromagnetic fields have “morphogenetic” effects—in other words, effects that influence the form of a developing organism. In particular, some experiments have shown that the targeted disturbance of these electric fields disrupts normal development in ways that suggest the fields are controlling morphogenesis.2 Artificially applied electric fields can induce and guide cell migration. There is also evidence that direct current can affect gene expression, meaning internally generated electric fields can provide spatial coordinates that guide embryogenesis.3 Although the ion channels that generate the fields consist of proteins that may be encoded by DNA (just as microtubules consist of subunits encoded by DNA), their pattern in the membrane is not. Thus, in addition to the information in DNA that encodes morphogenetic proteins, the spatial arrangement and distribution of these ion channels influence the development of the animal.

The Sugar Code
These sequence-specific information-rich structures influence the arrangement of different cell types during embryological development. Thus, some cell biologists now refer to the arrangements of sugar molecules as the “sugar code” and compare these sequences to the digitally encoded information stored in DNA. As biochemist Hans-Joachim Gabius notes, sugars provide a system with “high-density coding” that is “essential to allow cells to communicate efficiently and swiftly through complex surface interactions.” According to Gabius, “These [sugar] molecules surpass amino acids and nucleotides by far in information-storing capacity.” So the precisely arranged sugar molecules on the surface of cells clearly represent another source of information independent of that stored in DNA base sequences.  These cascades are, along with the cell event itself, associated with the “coding information” on a cell surface, or, using another terminology, are realized due to an instruction for the cell from the morphogenetic field of an organism. The concrete signal transduction pathways connecting the "coding information" on a cell surface and the expression of the given sets of genes need to be elucidated. 

Above and beyond: epigenetic information 
genes alone do not determine the three-dimensional form and structure of an animal.  Developmental biologists, in particular, are now discovering more and more ways that crucial information for building body plans is imparted by the form and structure of embryonic cells, including information from both the unfertilized and fertilized egg. DNA helps direct protein synthesis. Parts of the DNA molecule also help to regulate the timing and expression of genetic information and the synthesis of various proteins within cells. Yet once proteins are synthesized, they must be arranged into higher-level systems of proteins and structures.
The three-dimensional structure or spatial architecture of embryonic cells plays important roles in determining body-plan formation during embryogenesis. Developmental biologists have identified several sources of epigenetic information in these cells.

Stephen C. Meyer, Darwin's doubt:
Neo darwinism and the challenge of epigenetic information 
These different sources of epigenetic information in embryonic cells pose an enormous challenge to the sufficiency of the neo-Darwinian mechanism. According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both body-plan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn’t wholly responsible for the way an embryo develops— for body-plan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand. Even in a best-case scenario—one that ignores the immense improbability of generating new genes by mutation and selection—mutations in DNA sequence would merely produce new genetic information. But building a new body plan requires more than just genetic information. It requires both genetic and epigenetic information—information by definition that is not stored in DNA and thus cannot be generated by mutations to the DNA. It follows that the mechanism of natural selection acting on random mutations in DNA cannot by itself generate novel body plans, such as those that first arose in the Cambrian explosion.

" Junk DNA "
MicroRNAs--"Once Dismissed as Junk"--Confirmed To Have Important Gene Regulatory Function

In 2008 Scientific American noted that microRNAs were "once dismissed as junk" and said the following:
Tiny snippets of the genome known as microRNA were long thought to be genomic refuse because they were transcribed from so-called "junk DNA," sections of the genome that do not carry information for making proteins responsible for various cellular functions. Evidence has been building since 1993, however, that microRNA is anything but genetic bric-a-brac. Quite the contrary, scientists say that it actually plays a crucial role in switching protein-coding genes on or off and regulating the amount of protein those genes produce.

Transposons and Retrotransposons
striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.

Principal Meanings of Evolution in Biology Textbooks 1

What is fact :
1. Change over time; history of nature; any sequence of events in nature
2. Changes in the frequencies of alleles in the gene pool of a population
3. Limited common descent: the idea that particular groups of organisms have descended from
a common ancestor.
4. The mechanisms responsible for the change required to produce limited descent with modification; chiefly natural selection acting on random variations or mutations

What is not fact: 
5. Universal common descent: the idea that all organisms have descended from a single common ancestor.
6. Blind watchmaker thesis: the idea that all organisms have descended from common ancestors through unguided, unintelligent, purposeless, material processes such as natural
selection acting on random variations or mutations; the idea that the Darwinian mechanism of natural selection acting on random variation, and other similarly naturalistic mechanisms, completely suffice to explain the origin of novel biological forms and the appearance of design in complex organisms.

1. Neo-Darwinism and the Modern Synthesis propose a gene-centric view, a scientific metabiological proposal going back to Darwin's landmark book " On the origin of species " in 1859, where first natural selection was proposed as the mechanism of biodiversity, and later,  gene variation defining how bodies are built and organized.

2. Science researchers have discovered, that robust networks of interactions and biological function, major morphological innovation, development and body form are based on integrative mechanisms, the interplay of genes with the gene regulatory network, Transposons and Retrotransposons, so-called Junk DNA, splicing, and over a dozen epigenetic codes, Membrane targets and patterns, Cytoskeletal arrays, Centrosomes, Ion channels, Sugar molecules on the exterior of cells (the sugar code), that are not specified by nuclear DNA - that is, inheritance is not defined through DNA sequences alone.

3. Science is coming to recognize, that none of the recently proposed alternatives, like the third way, Saltationism, Saltatory ontogeny, mutationism, Genetic drift, or combined theories, do full justice by taking into account all organizational biophysiological hierarchy and complexity which empirical science has come to discover. As such, only a holistic view, namely structuralism,  takes into consideration all influences that form cell form and size, body development and growth, doing justice to the scientific evidence.

4. Scrutinizing which causes ultimately respond for the complexity discovered in life is only satisfying, once the epistemologically flawed foundation of methodological naturalism is taken out of the box, and replaced by a new paradigm, where all possible mechanisms and causal influences are permitted to be scrutinized, investigated, and scientifically tested, including the interaction and creative force of an external intelligent, mental agency outside the known physical world, which through its transcendent power creates, forms and builds all physiobiological lifeforms in all its astounding diversity.

If the mechanisms as proposed by the modern extended evolutionary synthesis are insufficient, then it has to be figured out what OTHER mechanisms define body architecture, grow, differentiation, phenotype, and body form, and THEN it can be evaluated, how the origin of these mechanisms are best explained. As it comes out, the BIG contributor to explain life and its complexity is INFORMATION. Instructional, complex, specified, codified information that acts like a blueprint ( genes ), but also information that is PRE-PROGRAMMED and stored in epigenetic cell features on a structural level, which is pre-instructed to respond to environmental cues, development, and nutrition demands, and they are apt to communicate, crosstalk, signal, regulate, govern, control, recruit, interpret, recognize, orchestrate, elaborate strategies, guide and so forth.

1. Cells use sophisticated information transmission and amplification systems (signalling pathways), information interpretation, combination and selection ( the Gene regulatory network ) encoding and transcription ( DNA & RNA polymerase machines ) transmission (mRNA), and decoding ( Ribosome ) systems.
2. Setup of information transmission systems, aka.  transmission, amplification, interpretation, combination, selection, encoding, transmission, and decoding are always a deliberate act of intelligence
3. The existence of the genetic information transmission system is best explained by the implementation of an intelligent designer.

Meyer, Darwins doubt, page 212:
According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both body-plan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn’t wholly responsible for the way an embryo develops— for body-plan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand.

Even in a best-case scenario—one that ignores the immense improbability of generating new genes by mutation and selection—mutations in DNA sequence would merely produce new genetic information. But building a new body plan requires more than just genetic information. It requires both genetic and epigenetic information—information by definition that is not stored in DNA and thus cannot be generated by mutations to the DNA. It follows that the mechanism of natural selection acting on random mutations in DNA cannot by itself generate novel body plans, such as those that first arose in the Cambrian explosion.


http://reasonandscience.catsboard.com/t2316-where-do-complex-organisms-come-from

1. http://www.jodkowski.pl/ke/Meanings2000.pdf
2.http://reasonandscience.catsboard.com/t1390-macroevolution#1982



Last edited by Admin on Wed Oct 09, 2019 1:52 pm; edited 99 times in total

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2Evolution: Where Do Complex Organisms Come From? Empty DEVELOPMENTAL GENE REGULATORY NETWORKS on Sun Mar 06, 2016 8:22 am

Admin


Admin
Where Do Complex Organisms Come From?
http://reasonandscience.catsboard.com/t2316-where-do-complex-organisms-come-from

Here I outline in red, each of the 17 mechanisms, and quote science papers which affirm the relevance of the mechanism to explain organismal development, architecture, and complexity, and as such, science falsifies darwins gene-centric view, that mutations, natural selection, gene flow and drift explain biodiversity and organismal complexity:

1. The Gene regulation network orchestrates gene expression
2. Various signalling pathways generate Cell types and patterns
3. At least 23 Epigenetic Codes are multidimensional and perform various tasks essential to cell structure and development
4. Cell-Cell communication in various forms, especially important for animal development
5. Chromatin dance in the nucleus through extensile motors affect transcription and gene regulation
6. Post-transcriptional modifications (PTMs) of histones affect gene transcription
7. The DNA methylation code is like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on.
8. Homeobox and Hox genes determine the shape of the body.
9. Noncoding DNA  ( Junk DNA ) is transcribed into functional non-coding RNA molecules and switches protein-coding genes on or off.
10.  Transposons and Retrotransposons regulate genes
11. Centrosomeplay a central role in development
12. The precise arrangement of Cytoskeletal arrays provides critical structural information.
13. Membrane targets provide crucial information—spatial coordinates—for embryological development.
14. Ion Channels and Electromagnetic Fields influence the form of a developing organism
15. The Sugar Code forms information-rich structures which influence the arrangement of different cell types during embryological development.
16. Egg-polarity genes encode macromolecules deposited in the egg to organize the axes
17. Hormones  are special chemical messengers for development



1. The Gene regulation network orchestrates gene expression

EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY
Eric H. Davidson 2011 Feb 12
The neo-Darwinism ‘erroneously assumes that change in protein coding sequence is the basic cause of change in developmental program; and it erroneously assumes that evolutionary change in body plan morphology occurs by a continuous process. All of these assumptions are basically counterfactual.’
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135751/

2. Various signalling pathways generate Cell types and patterns

- Hedgehog (Hh)
The Hedgehog (Hh) pathway plays a central role in the development of most tissues and organs in mammals.
https://www.sciencedirect.com/science/article/pii/S0929664615000340  

- Wingless related (Wnt)
Almost 40 years of basic research in different model systems have painted a picture of a signalling cascade that is absolutely essential for the development of all multicellular animals, and for the growth and maintenance of various adult tissues.
http://dev.biologists.org/content/145/12/dev165902  


- Transforming growth factor-β (TGF-β)
The TGF-beta family of cytokines are ubiquitous, multifunctional and essential to survival. They play important roles in growth and development, inflammation and repair and host immunity.
https://www.ncbi.nlm.nih.gov/pubmed/9611771

- Receptor tyrosine kinase (RTK)
Receptor tyrosine kinases (RTKs) are essential components of signaling transduction that mediate cell-to-cell communication.
https://www.sinobiological.com/receptor-tyrosine-kinase-rtk-signaling-transduction.html

- Notch
Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway.
http://dev.biologists.org/content/138/17/3593

- Janus kinase (JAK)/signal transducer  
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for transducing signals from a variety of metabolically relevant hormones and cytokines including growth hormone, leptin, erythropoietin, IL4, IL6 and IFNγ.
https://www.cell.com/trends/endocrinology-metabolism/pdf/S1043-2760(17)30150-9.pdf

- Activators of transcription (STAT) protein kinases
Cytokines play a critical role in the normal development and function of the immune system. On the other hand, many rheumatologic diseases are characterized by poorly controlled responses to or dysregulated production of these mediators. Over the past decade tremendous strides have been made in clarifying how cytokines transmit signals via pathways using the Janus kinase (Jak) protein tyrosine kinases and the Signal transducer and activator of transcription (Stat) proteins.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC129988/

- Nuclear hormone pathways
Thyroid hormones control various aspects of gut development and homeostasis. The best-known example is in gastrointestinal tract remodeling during amphibian metamorphosis. It is well documented that these hormones act via the TR nuclear receptors, which are hormone-modulated transcription factors. Several studies have shown that thyroid hormones regulate the expression of several genes in the Notch signaling pathway, indicating a possible means by which they participate in the control of gut physiology.
http://dev.biologists.org/content/142/16/2764

- Bone morphogenetic proteins (BMP)
Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-β (TGF-β) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems.
https://www.ncbi.nlm.nih.gov/pubmed/25401122


- Epidermal growth factor receptors (EGFR)
EGFR signaling is crucial for the development of several organs including skin (reviewed in Ref. 116). EGFR signaling is especially crucial to keratinocyte migration and proliferation during wound healing.
https://www.sciencedirect.com/topics/medicine-and-dentistry/epidermal-growth-factor-receptor

- Fibroblast growth factors (FGF)
Fibroblast growth factors (FGFs) are a family of structurally related polypeptides that are essential for embryonic development and that function postnatally as homoeostatic factors, in the response to injury, in the regulation of electrical excitability of cells and as hormones that regulate metabolism.
https://academic.oup.com/jb/article/149/2/121/837258

- DNA methylation
An appropriate DNA methylation is critical in development. Indeed, a precise temporal and spatial pattern of early gene expression is mandatory for a normal embryogenesis.
https://www.ncbi.nlm.nih.gov/pubmed/23877618

- Histone modification and incorporation of histone variants
Variants have a crucial role in chromosome segregation, transcriptional regulation, DNA repair, and other processes.
https://www.researchgate.net/publication/270654681_Histone_Variants_and_Epigenetics

- Chromatin remodelling in Eukaryotic Cells
Chromatin remodelling is an important mechanism of regulating eukaryotic gene expression, which makes tightly condensed DNA
https://www.news-medical.net/life-sciences/Chromatin-Remodeling-Mechanisms-and-Importance.aspx

- Non-coding RNA-mediated epigenetic regulation
Epigenetic related ncRNAs include miRNA, siRNA, piRNA and lncRNA. In general, ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level.
https://www.whatisepigenetics.com/non-coding-rna/

3. Epigenetic Codes perform various tasks essential to cell structure and development

The Genetic Code
The Genomic regulatory Code
The Splicing Codes
The Metabolic Code
The Signal Transduction Codes
The Signal Integration Codes
The Histone Code
The Tubulin Code
The Sugar Code
The Glycomic Code
The non-ribosomal code
The Calcium Code
The RNA code
A domain substrate specificity code of Nonribosomal peptide synthetases (NRPS)
The DNA methylation Code
The coactivator/corepressor/epigenetic code
The transcription factor code
The post-translational modification code for transcription factors
The HOX Code
The Synaptic Adhesive Code
The Apoptosis Code
The Ubiquitin Code
The bioelectric code
The transcriptional cis-regulatory code
The phosphorylation code

4. Cell-Cell communication in various forms, especially important for animal development

Genes involved in Cell-Cell communication and transcriptional control are especially important for animal development
What are the genes that animals share with one another but not with other kingdoms of life? These would be expected to include genes required specifically for animal development but not needed for unicellular existence. Comparison of animal genomes with the genome of budding yeast—a unicellular eukaryote— suggests that three classes of genes are especially important for multicellular organization.

The first class includes genes that encode proteins used for cell-cell adhesion and cell signalling; hundreds of human genes encode signal proteins, cell-surface receptors, cell adhesion proteins, or ion channels that are either not present in yeast or present in much smaller numbers.

The second class includes genes encoding proteins that regulate transcription and chromatin structure: more than 1000 human genes encode transcription regulators, but only about 250 yeast genes do so. The development of animals is dominated by cell-cell interactions and by differential gene expression.

The third class of noncoding RNAs has a more uncertain status: it includes genes that encode microRNAs (miRNAs); there are at least 500 of these in humans. Along with the regulatory proteins, they play a significant part in controlling gene expression during animal development, but the full extent of their importance is still unclear.
Molecular Biology of the Cell, 5th Ed, 2008: page 1308

5. Chromatin dance in the nucleus through extensile motors affect transcription and gene regulation

Transcription and gene regulation Genome topology has emerged as a key player in all genome functions. Although a contribution of local genome looping in transcription has long been appreciated, recent observations have revealed the importance of long-range interactions, and genome-wide studies have uncovered the universal nature of such regulatory genome topology interactions in gene regulation. Several types of chromosomal interactions, either in the form of loops between sequences on the same chromosomes or interchromosomal interactions, have emerged as key mechanisms in gene regulationThe nature of genome topology is very precise, and so its regulatory functions in gene expression and genome maintenance. The emerging picture is one of extensive self-enforcing feedback between activity and spatial organization of the genome, suggestive of a self-organizing and self-perpetuating system that uses epigenetic dynamics to regulate genome function in response to regulatory cues and to propagate cell-fate memory
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837811/

6. Post-transcriptional modifications (PTMs) of histones affect gene transcription

According to the histone code hypothesis, the pattern of histone modification is recognized by proteins much like a language or code. One pattern of histone modification may attract proteins that inhibit transcription. Alternatively, a different combination of histone modifications may attract proteins, such as ATP-dependent chromatin-remodeling complexes, that promote gene transcription. In this way, the histone code plays a key role in accessing the information within the genomes of eukaryotic species. Post-translational modifications (PTMs) of histones provide a fine-tuned mechanism for regulating chromatin structure and dynamics.  In addition to combinatorial PTMs that function together both synergistically and antagonistically, there is now an appreciation for PTM asymmetry within individual nucleosomes, novel types of PTMs with unique functions, nucleosomes bearing histone variants, and nuclear compartmentalization events that are all contributing to the final output of chromatin organization and function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099259/

7. The DNA methylation code is like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on.

DNA methylation has several uses in the vertebrate cell. A very important role is to work in conjunction with other gene expression control mechanisms to establish a particularly efficient form of gene repression. This combination of mechanisms ensures that unneeded eukaryotic genes can be repressed to very high degrees. For example, the rate at which a vertebrate gene is transcribed can vary 10^6-fold between one tissue and another. The unexpressed vertebrate genes are much less “leaky” in terms of transcription than bacterial genes, in which the largest known differences in transcription rates between expressed and unexpressed gene states are about 1000-fold. DNA methylation helps to repress transcription in several ways. The methyl groups on methylated cytosines lie in the major groove of DNA and interfere directly with the binding of proteins (transcription regulators as well as the general transcription factors) required for transcription initiation. In addition, the cell contains a repertoire of proteins that bind specifically to methylated DNA.The best characterized of these associate with histone modifying enzymes, leading to a repressive chromatin state where chromatin structure and DNA methylation act synergistically.  One reflection of the importance of DNA methylation to humans is the widespread involvement of “incorrect” DNA methylation patterns in cancer progression
Molecular Biology of the Cell, 5th Ed, 2008: Cell, page 467

8. Homeobox and Hox genes determine the shape of the body

This family of related genes determines the shape of the body. It subdivides the embryo along the head-to-tail axis into fields of cells that eventually become limbs and other structures.  Starting as a fertilized egg with a homogeneous appearance, an embryo made of skin, muscles, nerves and other tissues gradually arises through the division of cells. Long before most cells in the emerging body begin to specialize, however, a plan that designates major regions of the body-the head, the trunk, the tail and so on is established. This plan helps seemingly identical combinations of tissues arrange themselves into distinctly different anatomical structures, such as arms and legs. Individual genes mediate some of the developmental decisions involved in establishing the embryonic body plan.
https://www.jstor.org/stable/pdf/24996862.pdf?seq=1#page_scan_tab_contents

9. Noncoding DNA  ( Junk DNA ) is transcribed into functional non-coding RNA molecules and switches protein-coding genes on or off.

Fundamental importance in the regulation of mammalian gene expression programs, from transcriptional initiation, termination and stability, through recruitment of the exon-junction complex to the recruitment of chromatin remodelers through the spliceosome. Eukaryotic cells use a variety of strategies to control their transcriptional output that employ a large number of regulatory factors that, in turn, must be tightly regulated. Introns, as genetic entities or RNA segments ( previously held as junk ), facilitate or participate in this amazing regulation feat by sheltering information for small regulatory RNAs allowing for concerted expression of multiple molecules in a given context, influencing where and when a messenger RNA is spliced and translated, preventing or attenuating translation off context or, on the contrary, diversifying the type and function of the molecules produced depending on the internal and external environment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394429/


10.  Transposons and Retrotransposons regulate genes

Striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.
Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that have a significant impact on mammalian development and genome regulation.
http://dev.biologists.org/content/143/22/4101

11. Centrosomes play a central role in development

Centrosome integrity is critically important for successful fertilization and embryo development. In humans, the sperm contributes the dominant centrosomal material containing centrioles and centrosomal components onto which oocyte centrosomal proteins assemble after sperm incorporation to form the sperm aster that is essential for uniting sperm and oocyte pronuclei.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734160/

12. The precise arrangement of Cytoskeletal arrays provides critical structural information.

The three major cytoskeletal filaments are responsible for different aspects of the cell’s spatial organization and mechanical properties. Actin filaments determine the shape of the cell’s surface and are necessary for whole-cell locomotion; they also drive the pinching of one cell into two. Microtubules determine the positions of membrane-enclosed organelles, direct intracellular transport, and form the mitotic spindle that segregates chromosomes during cell division. Intermediate filaments provide mechanical strength. All of these cytoskeletal filaments interact with hundreds of accessory proteins that regulate and link the filaments to other cell components, as well as to each other. The accessory proteins are essential for the controlled assembly of the cytoskeletal filaments in particular locations, and they include the motor proteins, remarkable molecular machines that convert the energy of ATP hydrolysis into mechanical force that can either move organelles along the filaments or move the filaments themselves.
Molecular Biology of the Cell By Bruce Alberts 6th. ed. page 889

13. Membrane targets provide crucial information—spatial coordinates—for embryological development.

Preexisting membrane targets, already positioned on the inside surface of the egg cell, determine where these molecules will attach and how they will function. These membrane targets provide crucial information—spatial coordinates—for embryological development.
https://bio-complexity.org/ojs/index.php/main/article/viewFile/BIO-C.2014.2/BIO-C.2014.2


14. Ion Channels and Electromagnetic Fields influence the form of a developing organism

Experiments have shown that electromagnetic fields have “morphogenetic” effects—in other words, effects that influence the form of a developing organism. In particular, some experiments have shown that the targeted disturbance of these electric fields disrupts normal development in ways that suggest the fields are controlling morphogenesis. Artificially applied electric fields can induce and guide cell migration. There is also evidence that direct current can affect gene expression, meaning internally generated electric fields can provide spatial coordinates that guide embryogenesis. Although the ion channels that generate the fields consist of proteins that may be encoded by DNA (just as microtubules consist of subunits encoded by DNA), their pattern in the membrane is not. Thus, in addition to the information in DNA that encodes morphogenetic proteins, the spatial arrangement and distribution of these ion channels influence the development of the animal.

https://pure.tue.nl/ws/files/10243383/20151217_CO_Vanegas.pdf

15. The Sugar Code forms information-rich structures which influence the arrangement of different cell types during embryological development.

These sequence-specific information-rich structures influence the arrangement of different cell types during embryological development. Thus, some cell biologists now refer to the arrangements of sugar molecules as the “sugar code” and compare these sequences to the digitally encoded information stored in DNA. As biochemist Hans-Joachim Gabius notes, sugars provide a system with “high-density coding” that is “essential to allow cells to communicate efficiently and swiftly through complex surface interactions.” According to Gabius, “These [sugar] molecules surpass amino acids and nucleotides by far in information-storing capacity.” So the precisely arranged sugar molecules on the surface of cells clearly represent another source of information independent of that stored in DNA base sequences.  These cascades are, along with the cell event itself, associated with the “coding information” on a cell surface, or, using another terminology, are realized due to an instruction for the cell from the morphogenetic field of an organism. The concrete signal transduction pathways connecting the "coding information" on a cell surface and the expression of the given sets of genes need to be elucidated. 
https://www.ncbi.nlm.nih.gov/pubmed/15174156

16. Egg-polarity genes encode macromolecules deposited in the egg to organize the axes

- Splicing Code: Jon Lieff, M.D. about the 
As important as the DNA code is, the alternative RNA splicing is equally, or more, important. In fact, recent research shows that alternative splicing may be the critical source of evolutionary changes differentiating primates and humans from other creatures such as worms and flies with a similar number of genes.
http://jonlieffmd.com/blog/alternative-rna-splicing-in-evolution

17. Hormones  are special chemical messengers for development

The endocrine system provides an electrochemical connection from the hypothalamus of the brain to all the organs that control the body metabolism, growth and development, and reproduction.
https://en.wikibooks.org/wiki/Human_Physiology/The_endocrine_system


Following list, each of the 17 mechanisms, and quote of science papers which affirm the relevance of the mechanism to explain organismal development and architecture

http://reasonandscience.catsboard.com/t2316-evolution-where-do-complex-organisms-come-from#6645

Following are the list of peer-reviewed scientific papers that demonstrate the REAL mechanisms that replace Darwin's gene-centric theory of mutations, natural selection, gene drift & flow to explain organismal architecture and complexity. I outline each of the 17 mechanisms and quote science papers which affirm the relevance of the mechanism:

Evidence points to preprogrammed specifying - instructional complex INFORMATION ( blueprints ) encoded in various genetic and epigenetic languages and signalling communication networks as the true mechanisms responsible for major morphological architecture and innovation & adaptation, development and body form:

EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135751/

Hedgehog (Hh)
https://www.sciencedirect.com/science/article/pii/S0929664615000340  

Wingless related (Wnt)
http://dev.biologists.org/content/145/12/dev165902  

Transforming growth factor-β (TGF-β)
https://www.ncbi.nlm.nih.gov/pubmed/9611771

Receptor tyrosine kinase (RTK)
https://www.sinobiological.com/receptor-tyrosine-kinase-rtk-signaling-transduction.html

Notch
http://dev.biologists.org/content/138/17/3593


Janus kinase (JAK)/signal transducer  
https://www.cell.com/trends/endocrinology-metabolism/pdf/S1043-2760(17)30150-9.pdf

Activators of transcription (STAT) protein kinases
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC129988/

Nuclear hormone pathways
http://dev.biologists.org/content/142/16/2764

Bone morphogenetic proteins (BMP)
https://www.ncbi.nlm.nih.gov/pubmed/25401122


Epidermal growth factor receptors (EGFR)
https://www.sciencedirect.com/topics/medicine-and-dentistry/epidermal-growth-factor-receptor

Fibroblast growth factors (FGF)
https://academic.oup.com/jb/article/149/2/121/837258

DNA methylation
https://www.ncbi.nlm.nih.gov/pubmed/23877618

Histone modification and incorporation of histone variants
https://www.researchgate.net/publication/270654681_Histone_Variants_and_Epigenetics


Chromatin remodelling in Eukaryotic Cells
https://www.news-medical.net/life-sciences/Chromatin-Remodeling-Mechanisms-and-Importance.aspx

Non-coding RNA-mediated epigenetic regulation
https://www.whatisepigenetics.com/non-coding-rna/

3. Epigenetic Codes perform various tasks essential to cell structure and development

The Genetic Code
The Genomic regulatory Code
The Splicing Codes
The Metabolic Code
The Signal Transduction Codes
The Signal Integration Codes
The Histone Code
The Tubulin Code
The Sugar Code
The Glycomic Code
The non-ribosomal code
The Calcium Code
The RNA code
A domain substrate specificity code of Nonribosomal peptide synthetases (NRPS)
The DNA methylation Code
The coactivator/corepressor/epigenetic code
The transcription factor code
The post-translational modification code for transcription factors
The HOX Code
The Synaptic Adhesive Code
The Apoptosis Code
The Ubiquitin Code
The bioelectric code
The transcriptional cis-regulatory code
The phosphorylation code

4. Cell-Cell communication in various forms, especially important for animal development
Molecular Biology of the Cell, 5th Ed, 2008: page 1308

5. Chromatin dance in the nucleus through extensile motors affect transcription and gene regulation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837811/

6. Post-transcriptional modifications (PTMs) of histones affect gene transcription
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099259/

7. The DNA methylation code is like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on.
Molecular Biology of the Cell, 5th Ed, 2008: Cell, page 467

8. Homeobox and Hox genes determine the shape of the body
https://www.jstor.org/stable/pdf/24996862.pdf?seq=1#page_scan_tab_contents

9. Noncoding DNA  ( Junk DNA ) is transcribed into functional non-coding RNA molecules and switches protein-coding genes on or off.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394429/

10.  Transposons and Retrotransposons regulate genes
http://dev.biologists.org/content/143/22/4101

11. Centrosomes play a central role in development
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734160/

12. The precise arrangement of Cytoskeletal arrays provides critical structural information.
Molecular Biology of the Cell By Bruce Alberts 6th. ed. page 889

13. Membrane targets provide crucial information—spatial coordinates—for embryological development.
https://bio-complexity.org/ojs/index.php/main/article/viewFile/BIO-C.2014.2/BIO-C.2014.2


14. Ion Channels and Electromagnetic Fields influence the form of a developing organism
https://pure.tue.nl/ws/files/10243383/20151217_CO_Vanegas.pdf

15. The Sugar Code forms information-rich structures which influence the arrangement of different cell types during embryological development.
https://www.ncbi.nlm.nih.gov/pubmed/15174156

16. Egg-polarity genes encode macromolecules deposited in the egg to organize the axesSplicing Code: Jon Lieff, M.D. 
http://jonlieffmd.com/blog/alternative-rna-splicing-in-evolution

17. Hormones  are special chemical messengers for development
https://en.wikibooks.org/wiki/Human_Physiology/The_endocrine_system

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135751/
https://www.sciencedirect.com/science/article/pii/S0929664615000340 
http://dev.biologists.org/content/145/12/dev165902 
https://www.ncbi.nlm.nih.gov/pubmed/9611771
https://www.sinobiological.com/receptor-tyrosine-kinase-rtk-signaling-transduction.html
http://dev.biologists.org/content/138/17/3593
https://www.cell.com/trends/endocrinology-metabolism/pdf/S1043-2760(17)30150-9.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC129988/
http://dev.biologists.org/content/142/16/2764
https://www.ncbi.nlm.nih.gov/pubmed/25401122
https://www.sciencedirect.com/topics/medicine-and-dentistry/epidermal-growth-factor-receptor
https://academic.oup.com/jb/article/149/2/121/837258
https://www.ncbi.nlm.nih.gov/pubmed/23877618
https://www.researchgate.net/publication/270654681_Histone_Variants_and_Epigenetics
https://www.news-medical.net/life-sciences/Chromatin-Remodeling-Mechanisms-and-Importance.aspx
https://www.whatisepigenetics.com/non-coding-rna/
Molecular Biology of the Cell, 5th Ed, 2008: page 1308
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837811/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099259/
Molecular Biology of the Cell, 5th Ed, 2008: Cell, page 467
https://www.jstor.org/stable/pdf/24996862.pdf?seq=1#page_scan_tab_contents
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394429/
http://dev.biologists.org/content/143/22/4101
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734160/
Molecular Biology of the Cell By Bruce Alberts 6th. ed. page 889
https://bio-complexity.org/ojs/index.php/main/article/viewFile/BIO-C.2014.2/BIO-C.2014.2
https://pure.tue.nl/ws/files/10243383/20151217_CO_Vanegas.pdf
https://www.ncbi.nlm.nih.gov/pubmed/15174156
http://jonlieffmd.com/blog/alternative-rna-splicing-in-evolution
https://en.wikibooks.org/wiki/Human_Physiology/The_endocrine_system



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Stephen C Meyer , Darwin's doubt pg.268:
THE HIERARCHICAL ORGANIZATION OF GENETIC AND EPIGENETIC  INFORMATION
In addition to the information stored in individual genes and the information present in the integrated  networks of genes and proteins in dGRNs, animal forms exemplify hierarchical arrangements or layers of information-rich molecules, systems, and structures. For example, developing embryos require epigenetic information in the form of specifically arranged
 
(a) membrane targets and patterns, 
(b) cytoskeletal arrays, 
(c) ion channels, and 
(d) sugar molecules on the exterior of cells (the sugar code).

 
Much of this epigenetic information resides in the structure of the maternal egg and is inherited directly from membrane to membrane independently of DNA.  This three-dimensional structural information interacts with other information-rich molecules and systems of molecules to ensure the proper development of an animal. In particular, epigenetic information influences the proper positioning and thus the function of regulatory proteins (including  DNA-binding proteins), messenger RNAs, and various membrane components. Epigenetic information also influences the function of developmental gene regulatory networks. Thus, information at a higher structural level in the maternal egg helps to determine the function of both whole networks of genes and proteins (dGRNs) and individual molecules (gene products) at a lower level within a developing animal. Genetic information is necessary to specify the arrangement of amino acids in a protein or bases in an RNA molecule. Similarly, dGRNs are necessary to specify the location and/or function of many gene products. And, in a similar way, epigenetic information is necessary to specify the location and determine the function of lower-level molecules and systems of molecules, including the dGRNs themselves.  Furthermore, the role of epigenetic information provides just one of many examples of the hierarchical arrangement (or layering) of information-rich structures, systems, and molecules within animals. Indeed, at every level of the biological hierarchy, organisms require specified and highly improbable (information-rich) arrangements of lower-level constituents in order to maintain their form and function. Genes require specified arrangements of nucleotide bases; proteins require specified arrangements of amino acids; cell structures and cell types require specified arrangements of proteins or systems of proteins; tissues and organs require specific arrangements of specific cell types; and body plans require specialized arrangements of tissues and organs. Animal forms contain information-rich lower-level components (such as proteins and genes). But they also contain information-rich arrangements of those components (such as the arrangement of genes and gene products in dGRNs or proteins in cytoskeletal arrays or membrane targets). Finally, animals also exhibit information-rich arrangements of higher-level systems and structures (such as the arrangements of specific cell types, tissues, and organs that form specific body plans).
 
The highly specified, tightly integrated, hierarchical arrangements of molecular components and systems within animal body plans also suggest intelligent design. This is, again, because of our experience with the features and systems that intelligent agents—and only intelligent agents— produce. Indeed, based on our experience, we know that intelligent human agents have the capacity to generate complex and functionally specified arrangements of matter—that is, to generate specified complexity or specified information. Further, human agents often design information-rich hierarchies, in which both individual modules and the arrangement of those modules exhibit complexity and specificity—specified information. Individual transistors, resistors, and capacitors in an integrated circuit exhibit considerable complexity and specificity of design. Yet at a higher level of organization, the specific arrangement and connection of these components within an integrated circuit requires additional information and reflects further design (see Fig.below).
 
Evolution: Where Do Complex Organisms Come From? Inform11
 
Figure 14.2.

Conscious and rational agents have, as part of their powers of purposive intelligence, the capacity to design information-rich parts and to organize those parts into functional information-rich systems and hierarchies. We know of no other causal entity or process that has this capacity. Clearly, we have good reason to doubt that mutation and selection, self-organizational processes, or any of the other undirected processes cited by other materialistic evolutionary theories, can do so. Thus, based upon our present experience of the causal powers of various entities and a careful assessment of the efficacy of various evolutionary mechanisms, we can infer intelligent design as the best explanation for the origin of the hierarchically organized layers of information needed to build the animal forms that arose in the Cambrian period.
 
There is another remarkable aspect of the hierarchical organization of information in animal forms.  Many of the same genes and proteins play very different roles, depending upon the larger organismal  and informational context in which they find themselves in different animal groups. For example, the  same gene (Pax-6 or its homolog, called eyeless), helps to regulate the development of the eyes of fruit flies (arthropods) and those of squid and mice (cephalopods and vertebrates, respectively). Yet arthropod eyes exemplify a completely different structure from vertebrate or cephalopod eyes. The fruit fly possesses a compound eye with hundreds of separate lenses (ommatidia), whereas both mice and squid employ a camera-type eye with a single lens and retinal surface. In addition, although the eyes of squid and mice resemble each other optically (single lens, large internal chamber, single retinal surface), they focus differently. They undergo completely different patterns of development and utilize different internal structures and nerve connections to the visual centers of the brain. Yet the Pax-6 gene and its homologs play a key role in regulating the construction of all three of these different adult sensory structures. Moreover, evolutionary and developmental biologists have found that this pattern of "same genes, different anatomy" recurs throughout the bilaterian phyla, for features  as fundamental as appendages, segmentation, the gut, heart, and sense organs
 
Evolution: Where Do Complex Organisms Come From? Gene_e11
 
This pattern contradicts the expectations of textbook evolutionary theory. Neo-Darwinism predicts that disparate adult structures should be produced by different genes. This prediction follows directly from the neo-Darwinian assumption that all evolutionary (including anatomical) transformations begin with mutations in DNA sequences—mutations that are fixed in populations by natural selection, genetic drift, or other evolutionary processes. The arrow of causality flows one way from genes (DNA) to development to adult anatomy. Thus, if biologists observe different animal forms, it follows that they should expect that different genes will specify those forms during animal development. Given the profound differences between the fruit-fly compound eye and the vertebrate camera eye, neo-Darwinian theory would not predict that the "same" genes would be involved in building different eyes in arthropods and chordates.

DEVELOPMENTAL GENE REGULATORY NETWORKS

Darwins doubt, page 199

Another line of research in developmental biology has revealed a related challenge to the creative power of the neo-Darwinian mechanism. Developmental biologists have discovered that many gene products (proteins and RNAs) needed for the development of specific animal body plans transmit signals that influence the way individual cells develop and differentiate themselves. Additionally, these signals affect how cells are organized and interact with each other during embryological development. These signaling molecules influence each other to form circuits or networks of coordinated interaction, much like integrated circuits on a circuitboard. For example, exactly when a signaling molecule gets transmitted often depends upon when a signal from another molecule is received, which in turn affects the transmission of still others—all of which are coordinated and integrated to perform specific time-critical functions. The coordination and integration of these signaling molecules in cells ensures the proper differentiation and organization of distinct cell types during the development of an animal body plan. Consequently, just as mutating an individual regulatory gene early in the development of an animal will inevitably shut down development, so too will mutations or alterations in the whole network of interacting signaling molecules destroy a developing embryo. No biologist has explored the regulatory logic of animal development more deeply than Eric Davidson, at the California Institute of Technology. Early in his career, collaborating with molecular biologist Roy Britten, Davidson formulated a theory of “gene regulation for higher cells.”1 By “higher cells” Davidson and Britten meant the differentiated, or specialized, cells found in any animal after the earliest stages of embryological development. Davidson observed that the cells of an individual animal, no matter how varied in form or function, “generally contain identical genomes.” During the life cycle of an organism, the genomes of these specialized cells express only a small fraction of their DNA at any given time and produce different RNAs as a result. These facts strongly suggest that some animal-wide system of genetic control functions to turn specific genes on and off as needed throughout the life of the organism—and that such a system functions during the development of an animal from egg to adult as different cell types are being constructed.

When they proposed their theory in 1969, Britten and Davidson acknowledged that “little is known. . . of the molecular mechanisms by which gene expression is controlled in differentiated cells.” Nevertheless, they deduced that such a system must be at work. Given:

(1) that tens or hundreds of specialized cell types arise during the development of animals, and
(2) that each cell contains the same genome, they reasoned
(3) that some control system must determine which genes are expressed in different cells at different times to ensure the differentiation of different cell types from each other—some system-wide regulatory logic must oversee and coordinate the expression of the genome.

Davidson has dedicated his career to discovering and describing the mechanisms by which these systems of gene regulation and control work during embryological development. During the last two decades, research in genomics has revealed that nonprotein-coding regions of the genome control and regulate the timing of the expression of the protein-coding regions of the genome. Davidson has shown that the nonprotein-coding regions of DNA that regulate and control gene expression and the protein-coding regions of the genome together function as circuits. These circuits, which Davidson calls “developmental gene regulatory networks” (or dGRNs) control the embryological development of animals.

Evolution: Where Do Complex Organisms Come From? Gene_r10

On arriving at Caltech in 1971, Davidson chose the purple sea urchin, Strongylocentrotus purpuratus, as his experimental model system. The biology of S. purpuratus makes it an attractive laboratory subject: the species occurs abundantly along the Pacific coast, produces enormous quantities of easily fertilized eggs in the lab, and lives for many years. Davidson and his coworkers pioneered the technology and experimental protocols required to dissect the sea urchin’s genetic regulatory system. The remarkable complexity of what they found needs to be depicted visually. Figure 13.4a shows the urchin embryo as it appears six hours after development has begun (top left of diagram). This is the 16-cell stage, meaning that four rounds of cell division have already occurred (1 → 2 → 4 → 8 → 16). As development proceeds in the next four stages, both the number of cells and the degree of cellular specialization increases, until, at 55 hours, elements of the urchin skeleton come into focus. Figure 13.4b shows, corresponding to these drawings of embryo development, a schematic diagram with the major classes of genes (for cell and tissue types) represented as boxes, linked by control arrows. Last, Figure 13.4c shows what Davidson calls “the genetic circuitry” that turns on the specific biomineralization genes that produce the structural proteins needed to build the urchin skeleton. 2

This last diagram represents a developmental gene regulatory network (or dGRN), an integrated network of protein and RNA-signaling molecules responsible for the differentiation and arrangement of the specialized cells that establish the rigid skeleton of the sea urchin. Notice that, to express the biomineralization genes that produce structural proteins that make the skeleton, genes far upstream, activated many hours earlier in development, must first play their role. This process does not happen fortuitously in the sea urchin but via highly regulated and precise control systems, as it does in all animals. Indeed, even one of the simplest animals, the worm C. elegans, possessing just over 1,000 cells as an adult, is constructed during development by dGRNs of remarkable precision and complexity. In all animals, the various dGRNs direct what Davidson describes as the embryo’s “progressive increase in complexity”—an increase, he writes, that can be measured in “informational terms.” Davidson notes that, once established, the complexity of the dGRNs as integrated circuits makes them stubbornly resistant to mutational change—a point he has stressed in nearly every publication on the topic over the past fifteen years. “In the sea urchin embryo,” he points out, “disarming any one of
these subcircuits produces some abnormality in expression.” Developmental gene regulatory networks resist mutational change because they are organized hierarchically. This means that some developmental gene regulatory networks control other gene regulatory networks, while some influence only the individual genes and proteins under their control. At the center of this regulatory hierarchy are the regulatory networks that specify the axis and global form of the animal body plan during development. These dGRNs cannot vary without causing catastrophic effects to the organism. Indeed, there are no examples of these deeply entrenched, functionally critical circuits varying at all. At the periphery of the hierarchy are gene regulatory networks that specify the arrangements for smaller-scale features that can sometimes vary. Yet, to produce a new body plan requires altering the axis and global form of the animal. This requires mutating the very circuits that do not vary without catastrophic effects. As Davidson emphasizes, mutations affecting the dGRNs that regulate body-plan development lead to “catastrophic loss of the body part or loss of viability altogether.”3  He explains in more detail:

There is always an observable consequence if a dGRN subcircuit is interrupted. Since these consequences are always catastrophically bad, flexibility is minimal, and since the subcircuits are all interconnected, the whole network partakes of the quality that there is only one way for things to work. And indeed the embryos of each species develop in only one way.

ENGINEERING CONSTRAINTS


Davidson’s findings present a profound challenge to the adequacy of the neo-Darwinian mechanism. Building a new animal body plan requires not just new genes and proteins, but new dGRNs. But to build a new dGRN from a preexisting dGRN by mutation and selection necessarily requires altering the preexisting developmental gene regulatory network. (the very kind of change that  cannot arise without multiple coordinated mutations). In any case, Davidson’s work has also shown that such alterations inevitably have catastrophic consequences. Davidson’s work highlights a profound contradiction between the neo-Darwinian account of how
new animal body plans are built and one of the most basic principles of engineering—the principle of constraints. Engineers have long understood that the more functionally integrated a system is, the more difficult it is to change any part of it without damaging or destroying the system as a whole. Davidson’s work confirms that this principle applies to developing organisms in spades. The system of gene regulation that controls animal-body-plan development is exquisitely integrated, so that significant alterations in these gene regulatory networks inevitably damage or destroy the developing animal.

As Davidson explains, “Interference with expression of any [multiply linked dGRNs] by mutation or experimental manipulation has severe effects on the phase of development that they initiate. This accentuates the selective conservation of the whole subcircuit, on pain of developmental catastrophe” (Davidson and Erwin, “An Integrated View of Precambrian Eumetazoan Evolution”

But given this, how could a new animal body plan, and the new dGRNs necessary to produce it, ever evolve gradually via mutation and selection from a preexisting body plan and set of dGRNs? Davidson makes clear that no one really knows: “contrary to classical evolution theory, the processes that drive the small changes observed as species diverge cannot be taken as models for the evolution of the body plans of animals.” He elaborates:

Neo-Darwinian evolution . . . assumes that all process works the same way, so that evolution of enzymes or flower colors can be used as current proxies for study of evolution of the body plan. It erroneously assumes that change in protein-coding sequence is the basic cause of change in developmental program; and it erroneously assumes that evolutionary change in body-plan morphology occurs by a continuous process. All of these assumptions are basically counterfactual. This cannot be surprising, since the neo-Darwinian synthesis from which these ideas stem was a premolecular biology concoction focused on population genetics and . . . natural history, neither of which have any direct mechanistic import for the genomic regulatory systems that drive embryonic development of the body plan.

NOW AND THEN

Eric Davidson’s work, like that of Nüsslein-Volhard and Wieschaus, highlights a difficulty of obvious relevance to the Cambrian explosion. Typically, paleontologists understand the Cambrian explosion as the geologically sudden appearance of new forms of animal life. Building these forms requires new developmental programs—including both new early-acting regulatory genes and new developmental gene regulatory networks. Yet if neither early-acting regulatory genes nor dGRNs can be altered by mutation without destroying existing developmental programs (and thus animal form), then mutating these entities will leave natural selection with nothing favorable to select and the evolution of animal form will, at that point, terminate. Darwin’s doubt about the Cambrian explosion centered on the problem of missing fossil intermediates. Not only have those forms not been found, but the Cambrian explosion itself illustrates a profound engineering problem that fossil evidence does not address—the problem of building a new form of animal life by gradually transforming one tightly integrated system of genetic components and their products into another. 

Although evidence is all around us of a deep geological past, and of multifarious genealogical relationships among ourselves and the organisms we currently share the planet with, scientists still have only sketchy ideas about how complex living forms arose in the course of evolution. As James Shapiro described in a recent Huffington Post blog entry, there has been good progress in understanding how complex cells arose from simpler ones by cell mergers, or "symbiogenesis." But even "simple" cells are quite complex, and the origins of cellular life (aka "chemical evolution"; read more here), are far from settled.

What about the complex bodies and organs of animals and plants? This is what primarily concerned the nineteenth century naturalists Alfred Russel Wallace and Charles Darwin (neither of whom knew anything about the internal intricacies of cells, including the nature of their genes), as they pondered the transformations of life throughout its history. Their solution was "natural selection," the acquisition of new forms and functions in populations of organisms by small increments, over long times, with each gradual change being subject to the sieve of "adaptation." Was each heritable variation better suited to some pre-existing task? If so, its exemplars increased and multiplied. If not, their kind faded away.

While it may be an adequate scenario for the refinement of some already-existing characters -- the beaks of finches, color intensity of moths -- the "microevolutionary" process envisioned by Darwin and his successors does not account in any plausible way for "macroevolutionary" patterns such as the differences between oysters and grasshoppers, fish and birds. In fact, adaptationist gradualism, though still popular in some scientific circles, is increasingly questioned and found wanting by evolutionary biologists working in an expanded set of disciplines.

By incorporating embryonic development and its underlying physico-genetic processes into evolutionary theory, investigators are learning that abrupt alterations in body plan and other aspects of organismal form can occur in response to environmental change or gene mutation in ways that affect multiple members of a population and exhibit consistent patterns of inheritance. Furthermore, there is increasing emphasis on the resourcefulness of organisms and their ability to construct their own niches. Having a "phenotype" (the outward manifestation of biological identity), very different from that of one's progenitors is no longer considered disqualifying for survival.

Although the writings of Wallace and Darwin's predecessor Jean-Baptiste Lamarck anticipated some current ideas about the morphologically prolific processes of embryo generation ("Le pouvoir de la vie") and the active strivings of organisms for survival in their environmental settings ("L'influence des circonstances"), Darwin's less speculative approach encouraged readier acceptance of his ideas by other scientists and the educated public. (The playwright George Bernard Shaw, in the preface to Back to Methuselah, put it more sharply as "Why Darwin converted the crowd.") By specifying that the variations in organismal form and function sorted out by natural selection were entirely incremental, Darwin's theory could side-step any questions about how the altered forms actually arose. It also created an incentive to deny the relevance of the more profound changes (Darwin called them "sports") that were well known to arise in natural populations. This may have been the best that could be done circa 1850, but its retention in the so-called modern evolutionary synthesis a century later was a scandalous legacy of the banishment of developmental biology (embryology) from the synthesis, and the indifferent attitude of biological education regarding the physical sciences.

The physical science of Darwin's time, which provided a backdrop to his thinking, was dominated by Newton's concept that material bodies only change course in proportion to external forces that act on them. It also included the often more pertinent notion (e.g., for the molding of pliable materials) from Aristotle of matter changing position or shape only to the extent that it continues to be pushed. These ideas, however, did not pretend to account for the sudden reorganizational changes (freezing, melting, phase separation, compositional change) seen in complex chemically and mechanically active materials. We now recognize that the tissues of a developing embryo are indeed such non-Newtonian, non-Aristotelian materials. By the end of Darwin's life new physical theories were being put forward to explain abrupt and large-scale changes in such materials, and by extension, the character and transformations of organisms and their organs.

Here is a partial list of late nineteenth and early twentieth-century physical concepts that have proved relevant to developmental processes (with the phenomenon they explain, at least partly, in parentheses): dynamical systems (ability of cells having the same genome to switch between different "types"), phase separation of liquids (capacity of embryonic tissues to form several non-mixing layers), chemical oscillations (propensity of embryonic tissues to organize into tandem segments), "Turing-type" reaction-diffusion systems (the formation in tissues of regularly spaced structures like feather and hair buds, pigment stripes, or the bones of the limb skeleton). All or most of these processes (termed "mesoscale," being most relevant to objects the size and texture of cell clusters), along with several others, are harnessed and mobilized by the secreted products of specific genes during embryogenesis in every one of the animal phyla (e.g., arthropods, mollusks, nematodes, chordates and so forth).

What can the existence and action of such protean generative processes tell us about the origin of organismal complexity? First, let's look at some of the expectations of the natural selection-based modern synthesis: (i) the largest differences within given categories of multicellular organisms, the animals or plants, for example, should have appeared gradually, only after exceptionally long periods of evolution; (ii) the extensive genetic changes required to generate such large differences over such vast times would have virtually erased any similarity between the sets of genes coordinating development in the different types of organism; and (iii) evolution of body types and organs should continue indefinitely. Since genetic mutation never ceases, novel organismal forms should constantly be appearing.


All these predictions of the standard model have proved to be incorrect. The actual state of affairs however, are expected outcomes of the "physico-genetic" picture outlined above. Briefly, we now know that complex multicellular organisms appeared rapidly (on a geological time scale, i.e., two episodes of no more than 10-20 million years each), employing for developmental patterning not newly evolved genes, but genes that had evolved for entirely different functions in single-celled ancestors. Generation of novel complex forms was able to happen so rapidly because the genetic ingredients were already at hand, but in addition because the mesoscale physical processes described above also did not require an incremental sequence of steps to come into existence. Everything was in place for an organismal "big bang" once simple multicellular clusters had appeared.

Unlike the presumption of the standard model, however, the physico-genetic scenario for the origination of complex multicellular forms is not open-ended and limitless. As with any material organizational process (think waves and eddies in liquid water), the relevant physics can only elicit those structural motifs inherent to the material in question. Thus we should not expect to see, and indeed don't, the "endless forms" that Darwin invoked in The Origin of Species.

With a 19th century notion of incremental material transformations no longer relevant to comprehending the range of organismal variation that has appeared throughout the history of life on Earth, the other pillar of the standard model can be discarded along with it. Specifically, if, as affirmed by niche construction theory, phenotypically novel animals or plants can invent new modes of existence in novel settings, rather than succumbing to a struggle for survival in the niches of their origin, there is no need for cycles of selection for marginal adaptive advantage to be the default explanation for macroevolutionary change.

Additional reading

Newman, S.A. (2012). Physico-genetic determinants in the evolution of development. Science 338, 217-219.

Müller, G.B. (2007). Evo-devo: extending the evolutionary synthesis. Nature Reviews Genetic 8, 943-949.

Forgacs, G., and Newman, S.A. (2005). Biological physics of the developing embryo (Cambridge, Cambridge Univ. Press).

Odling-Smee, F.J., Laland, K.N., and Feldman, M.W. (2003). Niche construction: the neglected process in evolution (Princeton, N.J., Princeton University Press).
Follow Stuart A. Newman on Twitter: www.twitter.com/sanewman1

1) http://www.huffingtonpost.com/stuart-a-newman/complex-organisms_b_2240232.html
1) https://embryo.asu.edu/pages/gene-regulation-higher-cells-theory-1969-roy-j-britten-and-eric-h-davidson
2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2329687/
3) http://www.sciencedirect.com/science/article/pii/S0012160611000911?np=y
4) https://arxiv.org/ftp/arxiv/papers/1205/1205.1158.pdf

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Before we can understand what influences biological change, we need to know what influences biological development, cell structure, size, and form, and biological body architecture.

Every time, a proponent of evolution argues that a proponent of intelligent design does not know how evolution works, asking following will elucidate if the questioner himself actually meets the demand.

Which of the 23 items below does NOT define Cell and body form, size and shape, and organism development? If you cannot point it out, you demonstrate lack of knowledge to argue about if Darwins Theory is true,  and confirmed, or not:

Genetic:
1.DNA Code sequence

Epigenetic ( beyond or outside the genetic information ) :
1. Membrane targets and patterns
2. Cytoskeletal arrays
3. Centrosomes
4. Ion channels, and their location in the cell membrane
5. Sugar molecules on the exterior of cells (the sugar or glycan code)
6. Gene regulatory networks
7. Splicing Code
8. Metabolic Code
9. Signal Transduction Codes
10. Signal Integration Codes
11. Histone Code
12. Tubulin Code
13. Glycomic Code
14. Calcium Code
15. RNA Code
16. MicroRNAs
17. Transposons and Retrotransposons
18. DNA dinucleotide methylation
19. DNA CpG island methylation
20. Histone methylation
21. Chromatin remodeling
22. DNA coiling
23. microRNA regulation

The answer :
ALL of above 23 mentioned items ( and many more which science will discover ) do influence cell shape, body form, and development. There is just ONE item which is genetic, namely the genetic DNA sequence, which upon Mutation, migration (gene flow), genetic drift, and natural selection has influence in a VERY limited range.

I think, we, Creationists / ID-proponentists, have made it into a hobby, to point out why Darwins Theory is false. Above points it out in a nutshell, why. You can save this list on your laptop, and use it, every time when an atheist wishes to educate you on evolution.

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Replacing Darwins Theory of Evolution

Pinpointing what REALLY defines body architecture, the orchestration of organism development, cell shape and body form, and exposing the correct explanation of biochemical mechanisms of biodiversity is the holy grail of biological sciences

Preprogrammed codified information and signalling replaces Darwin's theory and its various subsequent adaptations, extensions, and new proposals like the modern extended synthesis. Some have also proposed a " third way ". Darwins Theory of Evolution to explain biodiversity can be replaced with

" Biochemical systems programming and signalling"

Following list is the result of years of my investigation. It is for sure not complete, ( there must be more mechanisms ), but I do not know of anyone else that has exposed a more complete framework. The only book I came across ( and has been part of my education ) Is Stephen C. Meyers: Darwin's doubt.

Where Do Complex Organisms Come From?
http://reasonandscience.catsboard.com/t2316-where-do-complex-organisms-come-from

- The Gene regulation network orchestrates gene expression
- Various signalling pathways generate Cell type and patterns
- Epigenetic Codes are multidimensional and perform various tasks essential to cell structure and development
- Cell-Cell communication in various forms, especially important for animal development
- Chromatin dance in the nucleus through extensile motors affect transcription and gene regulation
- Post-transcriptional modifications (PTMs) of histones affect gene transcription
- The DNA methylation code and language which, like a barcode or marker, the methyl group indicates which genes in the DNA are to be turned on.
- Homeobox and Hox genes determine the shape of the body.
- " Junk DNA "has a crucial role in switching the right protein-coding genes on or off
- Gene regulation through Transposons and Retrotransposons
- The precise arrangement of Cytoskeletal arrays
- Membrane targets which provide crucial information—spatial coordinates—for embryological development.
- Ion Channels and Electromagnetic Fields that influence the form of a developing organism
- The Sugar Code forms sequence-specific information-rich structures which influence the arrangement of different cell types during embryological development.
- Egg-polarity genes encode macromolecules deposited in the egg to organize the axes
- hormones

Almost everybody knows the main tenets of evolutionary biology and how it supposedly works: mutations by natural selection. And a few better informed know that it englobes genetic drift and gene flow. But nobody has empirical evidence that these mentioned mechanisms are in fact responsible to explain biodiversity. It is believed to be true, despite never been observed. The claim is that it takes long periods of time, therefore it is justified to claim that this IS the mechanism, despite not observed. Not true. Lenski's experiment with e.coli bacteria over decades and myriads of generations has never demonstrated bacterias to become something new.

The claim that science is still working on it is also false. Science has upon what I have researched a pretty good understanding on a holistic level, the true mechanisms are known, but not expressly mentioned because of the evolutionary underpinning and obsolete philosophical framework, where everything has to be pressed into evolutionary thinking. When put on the table, point by point, what defines body form, and analysed in a systemic approach, it becomes clear, that dozens of different mechanisms are in play.

But the BIG hero on the block which permeates all processes is preprogrammed information transmission and processing on a systemic level, stored in DNA, but principally epigenetic information and SIGNALLING in a myriad of forms and varieties. Information which is NOT stored in DNA, but epigenetic information systems, like the glycan Code on the cell surface which is more complex and permits far more information exchange and processing than DNA. Other at least 22 epigenetic codes are also involved in all kind of cellular processes, from defining WHEN certain biochemical processes have to occur, exactly how many cell divisions have to take place ( if the Cells in the human body would divide just ONE time more then necessary, we would look worse than Frankenstein ) Sex determination in mammals is determined by hormones, which are also signalling molecules. Adaptation to the environment depends on the transmission of signals to the chromosome, which instructs them what proteins have to be expressed to best adapt to the environmental conditions. The Cell cycle is entirely controlled with high precision by checkpoints which depend on getting the right signals to know when to permit the next stage to take place, and so on.

Signalling, pre-programmed information, and Code systems that permit send and transmit codified information and receivers that recognize and decode it correctly, and execute the right biochemical tasks to sustain life, that permit development of multicellular organisms in an orderly, orchestrated, precise fashion, and permit the organism to adapt to the environment upon received information through signalling, is undeniable evidence of a superintelligent mind, which did set it all up. Life was with extreme certainty, designed.

Evolution: Where Do Complex Organisms Come From? Worldv10

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Dembski and J.Wells: The design of life, general notes, page 16:

What Besides DNA Controls Development? If DNA does not control development, what does? Actually, there is good evidence for the involvement of at least two other factors in the developing egg: the cytoskeleton and the membrane. Every animal cell contains a network of microscopic fibers called a cytoskeleton. These fibers include microtubules, which are known to be involved in patterning embryos. For example, one of the gene products involved in head-to-rear patterning of fruit fly embryos is delivered to its proper location by microtubules; if the microtubules are experimentally disrupted, the gene product doesn’t reach its proper destination and the embryo is grossly deformed. Microtubules consist of many identical protein subunits, and each subunit is produced according to a template in the organism’s DNA. What matters in development is the organization of microtubule arrays, and the organization of a microtubule array is not determined by its subunits any more than the layout of a house is determined by its bricks. Instead, microtubule arrays are formed by organelles called centrosomes, which are inherited independently of an organism’s DNA. Centrosomes play a central role in development: a frog egg can be induced to develop into a frog merely by injecting a sperm centrosome—no sperm DNA is needed. Another non-genetic factor involved in development is the membrane pattern of the egg cell. 

Cell membranes are not merely featureless bags, but highly complex structures. For example, a membrane contains specialized channels that pump molecules in and out of the cell, enabling it to control its interactions with the external environment. An egg cell membrane also contains “targets” which ensure that molecules synthesized in the nucleus reach their proper destinations in the embryo. The gene product, which is involved in head-to-rear patterning of fruit fly embryos and which depends on microtubules to deliver it to its proper location, also needs a target molecule to keep it in place after it arrives. The target is already there, embedded in the membrane. Experiments with single-celled animals show that membrane patterns are determined by pre-existing membranes, not by DNA. Like microtubule subunits, the proteins embedded in a membrane are produced according to templates in the organism’s DNA; but like the form and location of microtubule arrays, the patterns of those embedded proteins are inherited independently of the organism’s DNA. So the control exercised by microtubule arrays and membrane patterns over embryonic development is not encoded in DNA sequences. This does not mean that we now understand developmental programs. Far from it! But it is quite clear that they cannot be reduced to genetic programs, written in the language of DNA sequences. It would be more accurate to say that a developmental program is written into the structure of the entire fertilized egg—including its DNA, microtubule arrays, and membrane patterns—in a language of which we are still largely ignorant.

EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY 1
Never in the modern history of evolutionary bioscience have such essentially different ideas about how to understand evolution of the animal body plan been simultaneously current. The first is the classic neo-Darwinian concept that evolution of animal morphology occurs by means of small continuous changes in primary protein sequence which in general require homozygosity to effect phenotype. The second paradigm holds that evolution at all levels can be illuminated by detailed analysis of cis-regulatory changes in genes that are direct targets of sequence level selection, in that they control variation of immediate adaptive significance. An entirely different way of thinking is that the evolution of animal body plans is a system level property of the developmental gene regulatory networks (dGRNs) which control ontogeny of the body plan.


http://reasonandscience.heavenforum.org/t2318-gene-regulatory-networks-controlling-body-plan-development#4804

In the years since, Wells has developed a powerful argument against the adequacy of the neo-Darwinian mechanism as an explanation for the origin of animal body plans. His argument turns on the importance of epigenetic information to animal development. To see why epigenetic information poses an additional challenge to neo-Darwinism and what exactly biologists mean by “epigenetic” information, let’s examine the relationship between biological form and biological information.
Stephen C Meyer , Darwin's doubt pg.11:

FORM AND INFORMATION
 Biologists typically define “form” as a distinctive shape and arrangement of body parts. Organismal forms exist in three spatial dimensions and arise in time—in the case of animals during development from embryo to adult. Animal form arises as material constituents are constrained to establish specific arrangements with an identifiable three-dimensional shape or “topography”—one that we would recognize as the body plan of a particular type of animal. A particular “form,” therefore, represents a highly specific arrangement of material components among a much larger set of possible arrangements. Understanding form in this way suggests a connection to the notion of information in its most theoretically general sense.  Shannon’s mathematical theory of information equated the amount of information transmitted with the amount of uncertainty reduced or eliminated in a series of symbols or characters. Information, in Shannon’s theory, is thus imparted as some options, or possible arrangements, are excluded and others are actualized. The greater the number of arrangements excluded, the greater the amount of information conveyed. Constraining a set of possible material arrangements, by whatever means, involves excluding some options and actualizing others. Such a process generates information in the most general sense of Shannon’s theory. It follows that the constraints that produce biological form also impart information, even if this information is notencoded in digital form.
 
DNA contains not only Shannon information but also functional or specified information. The arrangements of nucleotides in DNA or of amino acids in a protein are highly improbable and thus contain large amounts of Shannon information. But the function of DNA and proteins depends upon extremely specific arrangements of bases and amino acids. Similarly, animal body plans represent, not only highly improbable, but also highly specific
arrangements of matter. Organismal form and function depend upon the precise arrangement of various constituents as they arise during, or contribute to, embryological development. Thus, the specific arrangement of the other building blocks of biological form—cells, clusters of similar cell types, dGRNs, tissues, and organs—also represent a kind of specified or functional information. I noted that the ease with which Shannon’s information theory applies to molecular biology has sometimes led to confusion about the kind of information contained in DNA and proteins. It may have also created confusion about the places that specified information might reside in organisms. Perhaps because the information-carrying capacity of the gene can be so easily measured, biologists have often treated DNA, RNA, and proteins as the sole repositories of biological information. Neo-Darwinists have assumed that genes possess all the information necessary to specify the form of an animal. They have also assumed that mutations in genes will suffice to generate the new information necessary to build a new form of animal life. Yet if biologists understand organismal form as resulting from constraints on the possible arrangements of matter at many levels in the biological hierarchy—from genes and proteins, to cell types and tissues, to organs and body plans —then biological organisms may well exhibit many levels of information-rich structure. Discoveries in developmental biology have confirmed this possibility.


ABOVE AND BEYOND: EPIGENETIC INFORMATION
 In 2003, MIT Press published a groundbreaking collection of scientific essays titled Origination of Organismal Form: Beyond the Gene in Developmental and Evolutionary Biology, edited by two distinguished developmental and evolutionary biologists, Gerd Müller, of the University of Vienna, and Stuart Newman, of New York Medical College. In their volume, Müller and Newman included a number of scientific articles describing recent discoveries in genetics and developmental biology—discoveries suggesting that genes alone do not determine the three-dimensional form and structure of an animal. Instead, many of the scientists in their volume reported that so-called epigenetic information—information stored in cell structures, but not in DNA sequences—plays a crucial role. The Greek prefix epi means “above” or “beyond,” so epigenetics refers to a source of information that lies beyond the genes. As Müller and Newman explain in their introduction, “Detailed information at the level of the gene does not serve to explain form.” Instead, as Newman explains, “epigenetic” or “contextual information” plays a crucial role in the formation of animal “body assemblies” during embryological development. Müller and Newman not only highlighted the importance of epigenetic information to the formation of body plans during development; they also argued that it must have played a similarly important role in the origin and evolution of animal body plans in the first place. They concluded that recent discoveries about the role of epigenetic information in animal development pose a formidable challenge to the standard neo-Darwinian account of the origin of these body plans—perhaps the most formidable of all. In the introductory essay to their volume, Müller and Newman list a number of “open questions” in evolutionary biology, including the question of the origin of Cambrian-era animal body plans and the origin of organismal form generally, the latter being the central topic of their book. They note that though “the neo-Darwinian paradigm still represents the central explanatory framework of evolution,” it has “no theory of the generative.” In their view, neo-Darwinism “completely avoids [the question of] the origination of phenotypic traits and of organismal form.” As they and others in their volume maintain, neo-Darwinism lacks an explanation for the origin of organismal form precisely because it cannot explain the origin of epigenetic information. I first learned about the problem of epigenetic information and the Spemann and Mangold experiment while driving to a private meeting of Darwin-doubting scientists on the central coast of California in 1993. In the car with me was Jonathan Wells , who was then finishing a Ph.D. in developmental biology at the University of California at Berkeley. Like some others in his field, Wells had come to reject the (exclusively) “gene-centric” view of animal development and to recognize the importance of nongenetic sources of information. By that time, I had studied many questions and challenges to standard evolutionary theories arising out of molecular biology. But epigenetics was new to me. On our drive, I asked Wells why developmental biology was so important to evolutionary theory and to assessing neo-Darwinism. I’ll never forget his reply. “Because” he said, “that’s where the whole theory is going to unravel.”


BEYOND GENES
 Many biologists no longer believe that DNA directs virtually everything happening within the cell. Developmental biologists, in particular, are now discovering more and more ways that crucial information for building body plans is imparted by the form and structure of embryonic cells, including information from both the unfertilized and fertilized egg.Biologists now refer to these sources of information as “epigenetic.”10 Spemann and Mangold’s experiment is only one of many to suggest that something beyond DNA may be influencing the development of animal body plans. Since the 1980s, developmental and cell biologists such as Brian Goodwin, Wallace Arthur, Stuart Newman, Fred Nijhout, and Harold Franklin have discovered or analyzed many sources of epigenetic information. Even molecular biologists such as Sidney Brenner, who pioneered the idea that genetic programs direct animal development, now insist that the information needed to code for complex biological systems vastly outstrips the information in DNA. DNA helps direct protein synthesis. Parts of the DNA molecule also help to regulate the timing and expression of genetic information and the synthesis of various proteins within cells. Yet once proteins are synthesized, they must be arranged into higher-level systems of proteins and structures. Genes and proteins are made from simple building blocks—nucleotide bases and amino acids, respectively—arranged in specific ways. Similarly, distinctive cell types are made of, among other things, systems of specialized proteins. Organs are made of specialized arrangements of cell types and tissues. And body plans comprise specific arrangements of specialized organs. Yet the properties of individual proteins do not fully determine the organization of these higher-level structures and patterns. Other sources of information must help arrange individual proteins into systems of proteins, systems of proteins into distinctive cell types, cell types into tissues, and different tissues into organs. And different organs and tissues must be arranged to form body plans.
 
The hierarchical layering or arrangement of different sources of information. Note that the information necessary to build the lower-level electronic components does not determine the arrangement of those components on the circuit board or the arrangement of the circuit board and the other parts necessary to make a computer. That requires additional informational inputs. Two analogies may help clarify the point. At a construction site, builders will make use of many materials: lumber, wires, nails, drywall, piping, and windows. Yet building materials do not determine the floor plan of the house or the arrangement of houses in a neighborhood. Similarly, electronic circuits are composed of many components, such as resistors, capacitors, and transistors. But such lower-level components do not determine their own arrangement in an integrated circuit (see Fig. 14.2). In a similar way, DNA does not by itself direct how individual proteins are assembled into these larger systems or structures—cell types, tissues, organs, and body plans—during animal development.

Harold, “From Morphogenes to Morphogenesis,” 2774; Moss, What Genes Can’t Do. Of course, many proteins bind chemically with each other to form complexes and structures within cells. Nevertheless, these “self-organizational” properties do not fully account for higher levels of organization in cells, organs, or body plans. Or, as Moss has explained “Neither DNA nor any other aperiodic crystal constitutes a unique repository of heritable stability in the cell; in addition, the chemistry of the solid state does not constitute either a unique or even an ontologically or causally privileged basis for explaining the existence and continuity of order in the living world . . .” Moss, What Genes Can’t Do, 76.

Instead, the three-dimensional structure or spatial architecture of embryonic cells plays important roles in determining body-plan formation during embryogenesis. Developmental biologists have identified several sources of epigenetic information in these cells.
 
CYTOSKELETAL ARRAYS
Eukaryotic cells have internal skeletons to give them shape and stability. These “cytoskeletons” are made of several different kinds of filaments including those called the “microtubules.” The structure and location of the microtubules in the cytoskeleton influence the patterning and development of embryos. Microtubule “arrays” within embryonic cells help to distribute essential proteins used during development to specific locations in these cells. Once delivered, these proteins perform functions critical to development, but they can only do so if they are delivered to their correct locations with the help of preexisting, precisely structured microtubule or cytoskeletal arrays (see Figures below).

Thus, the precise arrangement of microtubules in the cytoskeleton constitutes a form of critical structural information. These microtubule arrays are made of proteins called tubulin, which are gene products. Nevertheless, like bricks that can be used to assemble many different structures, the tubulin proteins in the cell’s microtubules are identical to one another. Thus, neither the tubulin subunits, nor the genes that produce them, account for the differences in the shape of the microtubule arrays that distinguish different kinds of embryos and developmental pathways. Instead, the structure of the microtubule array itself is, once again, determined by the location and arrangement of its subunits, not the properties of the subunits themselves. Jonathan Wells explains it this way: “What matters in [embryological] development is the shape and location of microtubule arrays, and the shape and location of a microtubule array is not determined by its units.” For this reason, as University of Colorado cell biologist Franklin Harold notes, it is impossible to predict the structure of the cytoskeleton of the cell from the characteristics of the protein constituents that form that structure.

Another cell structure influences the arrangement of the microtubule arrays and thus the precise structures they form and the functions they perform. In an animal cell, that structure is called the centrosome (literally, “central body”), a microscopic organelle that sits next to the nucleus between cell divisions in an undividing cell. Emanating from the centrosome is the microtubule array that gives a cell its three-dimensional shape and provides internal tracks for the directed transport of organelles and essential molecules to and from the nucleus. During cell division the centrosome duplicates itself. The two centrosomes form the poles of the cell-division apparatus, and each daughter cell inherits one of the centrosomes; yet the centrosome contains no DNA. Though centrosomes are made of proteins—gene products—the centrosome structure is not determined by genes alone.
Another important source of epigenetic information resides in the two-dimensional patterns of proteins in cell membranes. When messenger RNAs are transcribed, their protein products must be transported to the proper locations in embryonic cells in order to function properly. Directed transport involves the cytoskeleton, but it also depends on spatially localized targets in the membrane that are in place before transport occurs. Developmental biologists have shown that these membrane patterns play a crucial role in the embryological development of fruit flies.

Membrane Targets
For example, early embryo development in the fruit fly Drosophila melanogaster requires the regulatory molecules Bicoid and Nanos (among others). The former is required for anterior (head) development, and the latter is required for posterior (tail) development. In the early stages of embryological development, nurse cells pump Bicoid and Nanos RNAs into the egg. (Nurse cells provide the cell that will become the egg—known as the oocyte—and the embryo with maternally encoded messenger RNAs and proteins.) Cytoskeletal arrays then transport these RNAs through the oocyte, where they become attached to specified targets on the inner surface of the egg. Once in their proper place—but only then—Bicoid and Nanos play critical roles in organizing the head-to-tail axis of the developing fruit fly. They do this by forming two gradients (or differential concentrations), one with Bicoid protein most concentrated at the anterior end and another with Nanos protein most concentrated at the posterior end. Insofar as both of these molecules are RNAs—that is, gene products—genetic information plays an important role in this process. Even so, the information contained in the bicoid and nanos genes does not by itself ensure the proper function of the RNAs and proteins for which the genes code. Instead, preexisting membrane targets, already positioned on the inside surface of the egg cell, determine where these molecules will attach and how they will function. These membrane targets provide crucial information—spatial coordinates—for embryological development.

Ion Channels and Electromagnetic Fields
Membrane patterns can also provide epigenetic information by the precise arrangement of ion channels—openings in the cell wall through which charged electrical particles pass in both directions. For example, one type of channel uses a pump powered by the energy-rich molecule ATP to transport three sodium ions out of the cell for every two potassium ions that enter the cell. Since both ions have a charge of plus one (Na+, K+), the net difference sets up an electromagnetic field across the cell membrane. 1 Experiments have shown that electromagnetic fields have “morphogenetic” effects—in other words, effects that influence the form of a developing organism. In particular, some experiments have shown that the targeted disturbance of these electric fields disrupts normal development in ways that suggest the fields are controlling morphogenesis.2 Artificially applied electric fields can induce and guide cell migration. There is also evidence that direct current can affect gene expression, meaning internally generated electric fields can provide spatial coordinates that guide embryogenesis.3 Although the ion channels that generate the fields consist of proteins that may be encoded by DNA (just as microtubules consist of subunits encoded by DNA), their pattern in the membrane is not. Thus, in addition to the information in DNA that encodes morphogenetic proteins, the spatial arrangement and distribution of these ion channels influences the development of the animal.

The Sugar Code
Biologists know of an additional source of epigenetic information stored in the arrangement of sugar molecules on the exterior surface of the cell membrane. Sugars can be attached to the lipid molecules that make up the membrane itself (in which case they are called “glycolipids”), or they can be attached to the proteins embedded in the membrane (in which case they are called “glycoproteins”). Since simple sugars can be combined in many more ways than amino acids, which make up proteins, the resulting cell surface patterns can be enormously complex. As biologist Ronald Schnaar explains, “Each [sugar] building block can assume several different positions. It is as if an A could serve as four different letters, depending on whether it was standing upright, turned upside down, or laid on either of its sides. In fact, seven simple sugars can be rearranged to form hundreds of thousands of unique words, most of which have no more than five letters.” These sequence-specific information-rich structures influence the arrangement of different cell types during embryological development. Thus, some cell biologists now refer to the arrangements of sugar molecules as the “sugar code” and compare these sequences to the digitally encoded information stored in DNA. As biochemist Hans-Joachim Gabius notes, sugars provide a system with “high-density coding” that is “essential to allow cells to communicate efficiently and swiftly through complex surface interactions.” According to Gabius, “These [sugar] molecules surpass amino acids and nucleotides by far in information-storing capacity.” So the precisely arranged sugar molecules on the surface of cells clearly represent another source of information independent of that stored in DNA base sequences.


First, we suggest that the geometry of the organism and its parts is coded by a molecular code located on the cell surfaces in such a way that, with each cell, there can be associated a corresponding matrix, containing this code. As a particular model, we propose coding by several types of oligosaccharide residues of glycoconjugates. 1 
1. During embryogenesis, each cell undergoes cell divisions, growth, movements (shifts) and expression of specific molecules according to a determinate plan, invariant for each living species. 
2. This determinate plan for development of an organism can be considered as a tree of cell events from the initial state of the first cell (zygote) to a final predetermined state of an organism, where under cell event we understand “developmental events”, such as cell divisions, cell growth (death), cell differentiation and cell shifts. 
3. This determinate plan is coded by a set of specific biological markers, which, most likely, may exist and be transmitted as a set of cell membrane markers. Our main assumption is that such a code may be provided by a pattern of short oligosaccharide residues of glycoproteins (glycoconjugates) on a cell surface, changing in time and space. It is possible that some other cell surface markers, e.g. specific proteins, may play this coding role; however, short oligosaccharide residues of glycoconjugates have several specific features which make them the most plausible substances for such coding.
4. The general laws for cell events (cell motion laws), namely, the dependence of cell events on coded and positional biological information, have to be the same for all living species, leading to different forms and shapes resulting from different sets of species-specific molecular parameters. Our main goal is to describe these cell motion laws. 
5. Cell motion laws can be mathematically formulated using the notion of a morphogenetic field.  It is important to note that, in the framework of our model, the cascades of specific molecular events that correlate with pattern formation (e.g. differential gene expression, directed protein traffic, etc.) appear not to be the reason for a cell event. Rather, these cascades are, along with the cell event itself, associated with the “coding information” on a cell surface, or, using another terminology, are realized due to an instruction for the cell from the morphogenetic field of an organism. The concrete signal transduction pathways connecting the "coding information" on a cell surface and the expression of the given sets of genes need to be elucidated. 

NEO-DARWINISM AND THE CHALLENGE OF EPIGENETIC INFORMATION
These different sources of epigenetic information in embryonic cells pose an enormous challenge to the sufficiency of the neo-Darwinian mechanism. According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both body-plan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn’t wholly responsible for the way an embryo develops— for body-plan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand. Even in a best-case scenario—one that ignores the immense improbability of generating new genes by mutation and selection—mutations in DNA sequence would merely produce new genetic information. But building a new body plan requires more than just genetic information. It requires both genetic and epigenetic information—information by definition that is not stored in DNA and thus cannot be generated by mutations to the DNA. It follows that the mechanism of natural selection acting on random mutations in DNA cannot by itself generate novel body plans, such as those that first arose in the Cambrian explosion.

GENE-CENTRIC RESPONSES
Many of the biological structures that impart important three-dimensional spatial information—such as cytoskeletal arrays and membrane ion channels—are made of proteins. For this reason, some biologists have insisted that the genetic information in DNA that codes for these proteins does account for the spatial information in these various structures after all. In each case, however, this exclusively “gene-centric” view of the location of biological information—and the origin of biological form—has proven inadequate. First, in at least the case of the sugar molecules on the cell surface, gene products play no direct role. Genetic information produces proteins and RNA molecules, not sugars and carbohydrates. Of course, important glycoproteins and glycolipids (sugar-protein and sugar-fat composite molecules) are modified as the result of biosynthetic pathways involving networks of proteins. Nevertheless, the genetic information that generates the proteins in these pathways only determines the function and structure of the individual proteins; it does not specify the coordinated interaction between the proteins in the pathways that result in the modification of sugars. More important, the location of specific sugar molecules on the exterior surface of embryonic cells plays a critical role in the function that these sugar molecules play in intercellular communication and arrangement. Yet their location is not determined by the genes that code for the proteins to which these sugar molecules might be attached. Instead, research suggests that protein patterns in the cell membrane are transmitted directly from parent membrane to daughter membrane during cell division rather than as a result of gene expression in each new generation of cells. Since the sugar molecules on the exterior of the cell membrane are attached to proteins and lipids, it follows that their position and arrangement probably result from membrane-to-membrane transmission as well. Consider next the membrane targets that play a crucial role in embryological development by attracting morphogenetic molecules to specific places on the inner surface of the cell. These membrane targets consist largely of proteins, most of which are mainly specified by DNA. Even so, many “intrinsically disordered” proteins fold differently depending on the surrounding cellular context. This context thus provides epigenetic information. Further, many membrane targets include more than one protein, and these multiprotein structures do not automatically self-organize to form properly structured targets. Finally, it is not only the molecular structure of these membrane targets, but also their specific location and distribution that determines their function. Yet the location of these targets on the inner surface of the cell is not determined by the gene products out of which they are made any more than, for example, the locations of the bridges across the River Seine in Paris are determined by the properties of the stones out of which they are made.Similarly, the sodium-potassium ion pumps in cell membranes are indeed made of proteins. Nevertheless, it is, again, the location and distribution of those channels and pumps in the cell membrane that establish the contours of the electromagnetic field that, in turn, influence embryological development. The protein constituents of these channels do not determine where the ion channels are located. Like membrane targets and ion channels, microtubules are also made of many protein subunits, themselves undeniably the products of genetic information. In the case of microtubule arrays, defenders of the gene-centric view do not claim that individual tubulin proteins determine the structure of these arrays. Nevertheless, some have suggested that other proteins, or suites of proteins, acting in concert could determine such higher-level form. For example, some biologists have noted that so-called helper proteins—which are gene products—called “microtubule associated proteins” (MAPs) help to assemble the tubulin subunits in the microtubule arrays. Yet MAPs, and indeed many other necessary proteins, are only part of the story. The locations of specified target sites on the interior of the cell membrane also help to determine the shape of the cytoskeleton. And, as noted, the gene products out of which these targets are made do not determine the location of these targets. Similarly, the position and structure of the centrosome—the microtubuleorganizing center—also influences the structure of the cytoskeleton. Although centrosomes are made of proteins, the proteins that form these structures do not entirely determine their location and form. As Mark McNiven, a molecular biologist at the Mayo Clinic, and cell biologist Keith Porter, formerly of the University of Colorado, have shown, centrosome structure and membrane patterns as a whole convey three-dimensional structural information that helps determine the structure of the cytoskeleton and the location of its subunits. Moreover, as several other biologists have shown, the centrioles that compose the centrosomes replicate independently of DNA replication: daughter centrioles receive their form from the overall structure of the mother centriole, not from the individual gene products that constitute them. Additional evidence of this kind comes from ciliates, large single-celled eukaryotic organisms. Biologists have shown that microsurgery on the cell membranes of ciliates can produce heritable changes in membrane patterns without altering the DNA. This suggests that membrane patterns (as opposed to membrane constituents) are impressed directly on daughter cells. In both cases—in membrane patterns and centrosomes—form is transmitted from parent three-dimensional structures to daughter three-dimensional structures directly. It is not entirely contained in DNA sequences or the proteins for which these sequences code. Instead, in each new generation, the form and structure of the cell arises as the result of both gene products and the preexisting three-dimensional structure and organization inherent in cells, cell membranes, and cyto-skeletons. Many cellular structures are built from proteins, but proteins find their way to correct locations in part because of preexisting three-dimensional patterns and organization inherent in cellular structures. Neither structural proteins nor the genes that code for them can alone determine the three-dimensional shape and structure of the entities they build. Gene products provide necessary, but not sufficient, conditions for the development of three-dimensional structure within cells, organs, and body plans. If this is so, then natural selection acting on genetic variation and mutations alone cannot produce the new forms that arise in the history of life.

EPIGENETIC MUTATIONS
When I explain this in public talks, I can count on getting the same question. Someone in the audience will ask whether mutations could alter the structures in which epigenetic information resides. The questioner wonders if changes in epigenetic information could supply the variation and innovation that natural selection needs to generate new form, in much the same way that neo-Darwinists envision genetic mutations doing so. It’s a reasonable thing to ask, but it turns out that mutating epigenetic information doesn’t offer a realistic way of generating new forms of life. First, the structures in which epigenetic information inheres—cytoskeletal arrays and membrane patterns, for example—are much larger than individual nucleotide bases or even stretches of DNA. For this reason, these structures are not vulnerable to alteration by many of the typical sources of mutation that affect genes such as radiation and chemical agent. Second, to the extent that cell structures can be altered, these alterations are overwhelmingly likely to have harmful or catastrophic consequences. The original Spemann and Mangold experiment did, of course, involve forcibly altering an important repository of epigenetic information in a developing embryo. Yet the resulting embryo, though interesting and illustrative of the importance of epigenetic information, did not stand a chance of surviving in the wild, let alone reproducing. Altering the cell structures in which epigenetic information inheres will likely result in embryo death or sterile offspring—for much the same reason that mutating regulatory genes or developmental gene regulatory networks also produces evolutionary dead ends. The epigenetic information provided by various cell structures is critical to body-plan development, and many aspects of embryological development depend upon the precise three-dimensional placement and location of these informationrich cell structures. For example, the specific function of morphogenetic proteins, the regulatory proteins produced by master regulatory (Hox) genes, and developmental gene regulatory networks (dGRNs) all depend upon the location of specific, information-rich, and preexisting cell structures. For this reason, altering these cell structures will in all likelihood damage something else crucial during the developmental trajectory of the organism. Too many different entities involved in development depend for their proper function upon epigenetic information for such changes to have a beneficial or even neutral effect.

DARWIN’S GROWING ANOMALY
With the publication of On the Origin of Species in 1859, Darwin advanced, first and foremost, an explanation for the origin of biological form. At the time, he acknowledged that the pattern of appearance of the Cambrian animals did not conform to his gradualist picture of the history of life. Thus, he regarded the Cambrian explosion as primarily a problem of incompleteness in the fossil record.
 Yet clearly a more fundamental problem now afflicts the whole edifice of modern neo-Darwinian theory. The neo-Darwinian mechanism does not account for either the origin of the genetic or the epigenetic information necessary to produce new forms of life. Consequently, the problems posed to the theory by the Cambrian explosion remain unsolved. But further, the central problem that Darwin set out to answer in 1859, namely the origin of animal form in general, remains unanswered—as Müller and Newman in particular have noted. Contemporary critics of neo-Darwinism acknowledge, of course, that preexisting forms of life can diversify under the twin influences of natural selection and genetic mutation. Known microevolutionary processes can account for small changes in the coloring of peppered moths, the acquisition of antibiotic resistance in different strains of bacteria, and cyclical variations in the size of Galápagos finch beaks. Nevertheless, many biologists now argue that neo-Darwinian theory does not provide an adequate explanation for the origin of new body plans or events such as the Cambrian explosion. For example, evolutionary biologist Keith Stewart Thomson, formerly of Yale University, has expressed doubt that large-scale morphological changes could accumulate by minor changes at the genetic level.38 Geneticist George Miklos, of the Australian National University, has argued that neo-Darwinism fails to provide a mechanism that can produce large-scale innovations in form and structure. Biologists Scott Gilbert, John Opitz, and Rudolf Raff have attempted to develop a new theory of evolution to supplement classical neo-Darwinism, which, they argue, cannot adequately explain large-scale macroevolutionary change. As they note:

Starting in the 1970s, many biologists began questioning its [neo-Darwinism’s] adequacy in explaining evolution. Genetics might be adequate for explaining microevolution, but microevolutionary changes in gene frequency were not seen as able to turn a reptile into a mammal or to convert a fish into an amphibian. Microevolution looks at adaptations that concern the survival of the fittest, not the arrival of the fittest. As Goodwin (1995) points out, “the origin of species—Darwin’s problem—remains unsolved.” Gilbert and his colleagues have tried to solve the problem of the origin of form by invoking mutations in genes called Hox genes, which regulate the expression of other genes involved in animal development. Notwithstanding, many leading biologists and paleontologists—Gerry Webster and Brian Goodwin, Günter Theissen, Marc Kirschner, and John Gerhart, Jeffrey Schwartz, Douglas Erwin, Eric Davidson, Eugene Koonin, Simon Conway Morris, Robert Carroll, Gunter Wagner, Heinz-Albert Becker and Wolf-Eckhart Lönnig, Stuart Newman and Gerd Müller, Stuart Kauffman, Peter Stadler, Heinz Saedler, James Valentine, Giuseppe Sermonti, James Shapiro and Michael Lynch, to name several—have raised questions about the adequacy of the standard neo-Darwinian mechanism, and/or the problem of evolutionary novelty in particular. 

The perspective of Eugene Koonin, a biologist at the National Center for Biotechnology Information at the National Institutes of Health, provides just one good example of this skepticism. Koonin, “The Origin at 150,” He argues: 
“The edifice of the modern synthesis has crumbled, apparently, beyond repair . . . The summary of the state of affairs on the 150th anniversary of the Origin is somewhat shocking. In the postgenomic era, all major tenets of the modern synthesis have been, if not outright overturned, replaced by a new and incomparably more complex vision of the key aspects of evolution. So, not to mince words, the modern synthesis is gone. What comes next? The answer suggested by the Darwinian discourse of 2009 is a postmodern state, not so far a postmodern synthesis. Above all, such a state is characterized by the pluralism of processes and patterns in evolution that defies any straightforward generalization.”


Evolution: Where Do Complex Organisms Come From? Kinesi10

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Among the key empirical insights are that phenotypic variation often involves changes in the gene regulatory machinery that alters the timing, location, amount or type of gene product. This modification of pre-existing developmental processes can bring about coordinated changes in suites of characters, effectively enabling diversification through the differential coupling and decoupling of phenotypic modules


1. https://royalsocietypublishing.org/doi/full/10.1098/rspb.2015.1019

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Where Do Complex Organisms Come From?

Pinpointing what REALLY defines body architecture, the orchestration of organism development, cell shape and body form and the mechanisms of adaptation and secondary speciation, and exposing the correct explanation of biochemical mechanisms of biodiversity is the holy grail of biological sciences. Preprogrammed codified information and signalling replaces Darwin's theory and its various subsequent adaptations, extensions, and new proposals like the modern extended synthesis or the so-called " third way ". The true mechanism is " Biochemical systems programming and signalling", and special creation of species and/or kinds by an intelligent powerful creator. Long periods of time and gradual, evolutionary development is not possible, face the fact that cells and organisms work like gigantic interlocked machines and factory complexes, where in any case, if one tiny part is missing, nothing goes. Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. No glycine amino acids, no pyrimidines, no DNA - no life. No Watson Crick base pair fine-tuning, no DNA - no life. No ribosomal mechanism for amino acid amide bondage, no proteins, no life. No nitrogenase enzymes to fix nitrogen in an energy demanding, triple bond breaking process, no ammonia, required to make amino acids - no nitrogen cycle - no advanced life. No chlorophylls, no absorption of light to start photosynthesis, no starch and glucose - cells will have no food supply to sustain complex organisms - no advanced life on earth. No rubisco, no fix of CO2, no hydrocarbons - no advanced life. No counterion in retinal, and rhodopsin could not receive visible light - and there would be no vision on earth by any organism.

1. Biological sciences have come to discover in the last decades that major morphological innovation, development and body form are based on at least 16 different, but integrative mechanisms, the interplay of genes with the gene regulatory network, Trans and Retrotransposons, so-called Junk DNA, gene splicing and recombination, and at least two dozen epigenetic informational code systems, some, like the glycan ( sugar) code, far more complex than the genetic code, on the membrane - exterior side of cells, Post-transcriptional modifications (PTMs) of histones, hormones, Ion Channels and Electromagnetic Fields that are not specified by nuclear DNA, Membrane targets and patterns, Cytoskeletal arrays, Centrosomes, and inheritance by cell memory which is not defined through DNA sequences alone.

2. These varied mechanisms orchestrate gene expression, generate Cell types and patterns, perform various tasks essential to cell structure and development, are responsible for important tasks of organismal development, affect gene transcription, switch protein-coding genes on or off,  determine the shape of the body, regulate genes, provide critical structural information and spatial coordinates for embryological development,  influence the form of a developing organism and the arrangement of different cell types during embryological development, organize the axes, and act as chemical messengers for development

3. Neo-Darwinism and the Modern Synthesis have proposed traditionally a gene-centric view, a scientific metabiological proposal going back to Darwin's " On the origin of species ", where first natural selection was proposed as the mechanism of biodiversity, and later,  gene variation defining how bodies are built and organized. Not even recently proposed alternatives, like the third way, neutral theory, inclusive fitness theory, Saltationism, Saltatory ontogeny, mutationism, Genetic drift, or combined theories, do full justice by taking into account all organizational physiological hierarchy and complexity which empirical science has come to discover.

4. Only a holistic view, namely structuralism and systems biology, take into account all influences that form cell form and size, body development and growth, providing adequate descriptions of the scientific evidence. The BIG ( umbrella ) contributor to explain organismal complexity is preprogrammed instructional complex INFORMATION encoded in various languages and communication through signalling through various signalling networks  that act  on a structural level, which are pre-instructed to respond to environmental cues, development, and nutrition demands, and they are apt to communicate, crosstalk, signal, regulate, govern, control, recruit, interpret, recognize, orchestrate, elaborate strategies, guide and so forth. All codes, blueprints, and languages are inventions by intelligence. Therefore, the genetic and epigenetic codes and signalling networks and the instructions to build cells and complex biological organisms were most likely created by an intelligent agency.


Biological cells and organisms are characterized by Irreducible complexity and hierarchical top-down systems interdependence, which is understood as irreducible functional systems complexity. And such is specified by genetic and epigenetic informational codes and signals, used to set up and create front-loaded instructional blueprints, which direct how bodies are built, but also how life can self-correct, adapt to the environment and evolve. It is perfectly comparable to how a blueprint instructs to make machines and factories, and industries. Such things come undoubtedly from preexisting intelligence.

To understand the major trends in animal diversity and if the various kinds of morphology are due to evolution, we must first understand how animal form is generated. As science has unravelled, the make of body form, phenotype, and organismal architecture is due to several genetic and principally, epigenetic interlocked and interconnected mechanisms. The modern, extended evolutionary synthesis does not take into consideration all relevant factors. Structuralism proposes that complex structure emerges holistically from the dynamic interaction of all parts of an organism. It denies that biological complexity can be reduced to natural selection, gene drift and gene flow, and argues that pattern formation is driven principally by multilevel processes that involve various functional units, working in an interdependent manner, pre-programmed to respond to ecological and environmental cues and conditions, food resource availability, and development programs.  Various genetic and epigenetic Codes, an integrated understanding of the structural and functional aspects of epigenetics and several signalling pathways, nuclear architecture during differentiation, chromatin organisation, morphogenetic fields, amongst many other mechanisms.

1. The Gene regulation network orchestrates gene expression
2. Various signalling pathways generate Cell types and patterns
3. At least 23 Epigenetic Codes are multidimensional and perform various tasks essential to cell structure and development
4. Cell-Cell communication in various forms, especially important for animal development
5. Chromatin dance in the nucleus through extensile motors affect transcription and gene regulation
6. Post-transcriptional modifications (PTMs) of histones affect gene transcription
7. The DNA methylation code is like a barcode or marker, the methyl group indicates, for instance, which genes in the DNA are to be turned on.
8. Homeobox and Hox genes determine the shape of the body.
9. Noncoding DNA  ( Junk DNA ) is transcribed into functional non-coding RNA molecules and switches protein-coding genes on or off.
10.  Transposons and Retrotransposons regulate genes
11. Centrosomeplay a central role in development
12. The precise arrangement of Cytoskeletal arrays provides critical structural information.
13. Membrane targets provide crucial information—spatial coordinates—for embryological development.
14. Ion Channels and Electromagnetic Fields influence the form of a developing organism
15. The Sugar Code forms information-rich structures which influence the arrangement of different cell types during embryological development.
16. Egg-polarity genes encode macromolecules deposited in the egg to organize the axes
17. Hormones  are special chemical messengers for development

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If not macroevolution, what explains organismal form and biodiversity?

Evolution: Where Do Complex Organisms Come From? 0011

Bauplan is a German term used in biology which was first introduced by Joseph Henry Woodger in 1945 and means ground plan or structural plan. 

Evolution: Where Do Complex Organisms Come From? 015
Joseph Henry Woodger ( 1894 –  1981) was a British theoretical biologist and philosopher of biology

Woodger's attempts to make biological sciences more rigorous and empirical was significantly influential to the philosophy of biology in the twentieth century. Karl Popper, the prominent philosopher of science, claimed: "Woodger... influenced and stimulated the evolution of the philosophy of science in Britain and in the United States as hardly anybody else".

Before we can ask about the mechanisms and the origin and maintenance of body plans, we need to ask what mechanisms are currently responsible for the development and organismal architecture, form, and cell shape. Once these questions are elucidated, we can go a step further and ask questions about the origins of body plans and their structure. 

1. http://sci-hub.tw/https://link.springer.com/article/10.1007/s12052-012-0424-z

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If 99,999999999% of all biologists, biochemists, chemists, cytologists, evolutionary biologists, geneticists, development biologists say, that evolution by mutations and natural selection, drift and gene flow explains organismal complexity and variety, and that common ancestry is true, and that it is a fact, it still does not mean, it is a fact.

It takes just one scientist to falsify a consense view, and claims made by the majority of scientists.

It took just one scientist, Louis Pasteur, to demonstrate that life can only come from life. Sait 150 years ago, it is still true today.

But today, there is not just one. There are thousands of scientists, as well Nobel prize winners in physiology and medicine, even decades ago, that have actually looked into the science, and have come to the conclusion that the evolutionary claim is simply not true.

So why are there so many diverging opinions ?

I think most biologists do specialize in one discipline or another, and rarely grasp the whole picture. There is a reason, that there are millions of science papers related to evolution, biology, and biochemistry out there.

The Cell city is composed of millions of molecular machines, each demonstrating a unique set of architecture and function. Whole metabolic and signalling pathways, more complex than the internet covering the whole earth. Dozens of epigenetic languages, one, the glycan code by far more complex than the genetic Code. We don't know and do not fully understand what the junk part of DNA does. Science has not even started to unravel the language used in signalling....

It would take the effort of millions of scientists, all work together as a team, with a common goal, to do a project like ENCODE , and still getting just a superficial grasp of the whole picture of the Cell city and on a even far more complex, on organismal level.

The ignorance gives room to various opinions, depending also on bias and preference.

But science has come a long way along. I think, even with the superficial and still small knowledge we have, compared to the complexity unravelled in the molecular world, some important, and paradigm shifting conclusions can be made, with affirmative certainty.

Far more than genetic information is required to make complex organisms and body form.

Where Do Complex Organisms Come From?

http://reasonandscience.catsboard.com/t2316-evolution-where-do-complex-organisms-come-from

Based on evidence seen in biochemistry on a molecular level, we can now say affirmatively and conclusively, that Darwins theory of evolution by natural selection in regards of first degree macroevolutionary level has been falsified.

The real mechanisms that explain biodiversity and complex organismal architecture is preprogrammed instructional complex INFORMATION encoded in various genetic and epigenetic languages and communication by various signalling codes through various signalling networks

That brings us to the origin by an intelligent designer.

1) phenotypic variation in a population, 2) differential reproductive success as a consequence of that variation, and 3) inheritance of said variation.

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Nobody has probably influenced natural sciences, and in special biology, more than Charles Darwin. His landmark book, On the origin of species, published in 1859, did not only influence how in the coming 160 years biologists did attempt to explain organismal complexity and biodiversity but, in special through the promotion of Darwins bulldog, Thomas Henry Huxley, the scientific framework of philosophical materialism was implemented in scientific circles, by the so-called X Club, late in the 19th century, and has persisted until today. Every scientific explanation had to be explained by natural means, no supernatural causes permitted. Before that, the most prolific fathers of science, from Isaac Newton to Maxwell, Boyle etc.,  and inventers of the greatest scientific discoveries were theists, mostly Christians, and they had no restriction nor any problem to acknowledge God as the creator and power behind the existence and creation of the physical world, and life. While never fully undisputed, Darwin's theory has come more and more under attack, in special amongst religious circles, which ever since have seen Darwin's theory as an attack on the biblical Genesis account, to which the theory stands in harsh opposition and contradicts it.

There is a consensus amongst biologists and professional scientists that the theory of evolution is true. And this is an argument brought forward numerous times when the issue is debated today. Nonetheless, the evidence does not prove the theory to be true beyond any reasonable doubt. In fact, several lines of evidence, and investigations in various fields of science, like palaeontology, biochemistry, biology, development biology, cytology etc. do not confirm the theory. In the current debate, opponents have mainly focussed on disproving the theory by demonstrating why the proposed mechanisms, in special mutations and natural selection, but also genetic drift, do not suffice to explain the extraordinary complexity seen in biology. That is the negative side. What about the positive side? What does actually replace evolution? What are the real mechanisms that explain organismal form and complexity?  Successive adaptations of the theory have done shy attempts to expand it and incorporate new recent findings. Alternative proposals have been made in recent years, like the third way.

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What mechanisms replace Darwins Theory of evolution?

Evolution: Where Do Complex Organisms Come From? 0011



Evolution: Where Do Complex Organisms Come From? 1215
Natural selection, genetic drift, and gene flow are the claimed mechanisms that cause changes in allele frequencies over time, resulting in evolution and diversity of all the living on the planet and organismal complexity. 

Evolution: Where Do Complex Organisms Come From? 12310
Over time, this explanation has come more and more under attack, not only by traditional opposers as creationists but as well by professional scientists.  

Evolution: Where Do Complex Organisms Come From? 115

First, we need to make an important distinction between micro and macroevolution.  Microevolution can be thought of as horizontal change, while macroevolution would involve vertical beneficial change in complexity.

Evolution: Where Do Complex Organisms Come From? 1234511
It is a common assertion, even held today by the majority of biologists, that microevolution leads to macroevolution. The article in Nature magazine, for example, claims in its conclusion remarks:

Evolution: Where Do Complex Organisms Come From? 12345611

Evolution: Where Do Complex Organisms Come From? 123411
Let's clarify: Organisms can and do adapt to their environment, which is often described as microevolution, but would be better described as adaptation. It is life essential and had to be fully set up when life began. Natural selection on a limited scale is a fact, but even in regards of adaptation or microevolution, not the main driving mechanism that explains it.  

Evolution: Where Do Complex Organisms Come From? 12345612
The points in question are that all life forms began with a common ancestor and then diverged in all life forms seen today, by means of evolutionary mechanisms, which include mutation and natural selection, genetic drift and gene flow.


But is that claim true ? And if not true, what mechanisms replaces it?

I will not focus on why evolution by mutations and natural selection does not suffice, but what replaces it.

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